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he Warcraft universe is a fictional universe in which a series of games and books published by Blizzard Entertainment are set. Players were first introduced to this universe in the original Warcraft: Orcs & Humans in Eastern Kingdoms of the planet Azeroth. Known worlds in the Warcraft universe include Azeroth, Draenor the Red World (later called Outland), Argus, K'aresh, and Xoroth. Contents [hide]

  * 1 Geography
  * 2 Playable races
        o 2.1 Alliance
              + 2.1.1 Humans
              + 2.1.2 Gnomes
              + 2.1.3 Night Elves
              + 2.1.4 Dwarves
              + 2.1.5 Draenei
        o 2.2 Horde
              + 2.2.1 Orcs
              + 2.2.2 Forsaken
              + 2.2.3 Tauren
              + 2.2.4 Blood Elves
              + 2.2.5 Trolls
  * 3 Media set in the Warcraft universe
        o 3.1 Computer games
        o 3.2 Tabletop games
        o 3.3 Collectible card games
        o 3.4 Books
        o 3.5 Film adaptation
        o 3.6 Comics
  * 4 References
  * 5 External links

[edit] Geography

The majority of media in the Warcraft universe takes place upon a planet called Azeroth. This planet has three continents, named the Eastern Kingdoms, Northrend (the world polar cap) and Kalimdor, all of which are separated by a giant ocean called the Great Sea. In the center of the Great Sea is an enormous, everlasting vortex called the Maelstrom (created as a result of a cataclysm that split the previous supercontinent of Kalimdor into the three current major landmasses).

The landmass of the Eastern Kingdom is the setting of the majority of the Warcraft stories. In Warcraft: Orcs & Humans, the Humans of the story belong to the Kingdom of Azeroth, which lies south of Khaz Modan and was the largest human kingdom at the time. In Warcraft II: Tides of Darkness, the human kingdom depicted was Azeroth's northern neighbour of Lordaeron, which successfully headed the old Alliance in fighting off the orcish invasion but later fell to the Scourge in Warcraft III: Reign of Chaos.

The continent of Kalimdor was introduced in Warcraft III: Reign of Chaos. Whereas Azeroth (the continent) can be described as the equivalent of medieval Europe, with highly traditional kingdoms with advanced cities, Kalimdor can be compared to the Americas at their time of discovery by Europeans, full of wild, unexplored lands. The geology of Kalimdor is similar to North America, with massive, ancient forests covering the Northern parts and vast deserts in the South.

The third continent, Northrend, is the northern polar cap of Azeroth and is the primary stronghold of the malevolent Undead Scourge. Northrend is featured in Warcraft III: Reign of Chaos and its expansion set Warcraft III: Frozen Throne, and will be featured in World of Warcraft: Wrath of the Lich King, the second expansion pack to World of Warcraft.

Second in importance to Azeroth is the planet of Draenor, now known as Outland, the original homeland of the Orcs and Ogres. The Eredar who refused to ally themselves with Sargeras and the Burning Legion fled to this planet and became known as the Draenei ("Exiled Ones" in their native tongue; Draenor being "home of the exiled"). Draenor was torn apart when an Orc shaman named Ner'zhul opened too many gateways to other worlds, when trying to escape the invading Alliance Armies coming from Azeroth, causing it to crumble and phase into the mysterious parallel dimension called the Twisting Nether, Home of the Demons. The remnants of the world are now known as Outland, and it features in Warcraft II: Beyond the Dark Portal, Warcraft III: The Frozen Throne, and most prominently in World of Warcraft's first expansion World of Warcraft: The Burning Crusade.

Other planets in the universe include Argus, the original home-world of the Eredar race; K'aresh, the original home-world of the Ethereal race and Xoroth, the home-world of the Nathrezim and Dreadsteeds. The planet of Azeroth has two moons, named White Lady (a physical manifestation of the mysterious Night Elf goddess Elune) and Blue Child. Draenor, after having been shattered into many pieces, currently has no known moons.

Places beyond the planets include the Great Dark Beyond, Warcraft's equivalent of outer space; the Emerald Dream, a dream-scape resembling what Azeroth would look like if animals or sentient races had never in any way altered it; an Elemental Plane where the elemental lieutenants of the malevolent deities called the Old Gods are banished; the Dark Below, a hellish, little-referenced underworld the canon of which is debatable, referenced to only in the earlier games; and the Twisting Nether, an astral plane between worlds, home to demons of all sorts, a chaotic and magical environment that overlaps with the Great Dark Beyond, yet is normally imperceptible to mortals.

[edit] Playable races

[edit] Alliance

[edit] Humans

Humans were introduced in Warcraft: Orcs & Humans. Throughout the first two Warcraft games, the human race was depicted as the archetypal European kingdom. In Warcraft and Warcraft II they were also depicted as religious; the Humans fought for the side of Heaven against the Hellish Orcs, though this was abandoned in the third game.

In Warcraft III: Reign of Chaos and Warcraft III: The Frozen Throne we see the human nation of Lordaeron, the nation which is depicted throughout the second game as the main protagonists. The nation is exposed to a plague of undeath which turns those infected into undead monsters who serve the will of the Lich King (Ner'zhul). The prince of Lordaeron, Arthas Menethil, also succumbs to the will of the Lich King and is instrumental in bringing about the downfall of his kingdom and, eventually, the invasion of the Burning Legion. He is one of the main characters of the third game and its expansion.

In World of Warcraft human characters begin the game in the kingdom of Stormwind, Lordaeron's southern counterpart. Skin and hair choices are restricted to realistic human tones.

The humans are descended from an ancient nomadic tribe known as the Arathi, who conquered and united the other warring human tribes and founded the nation of Arathor and the great city of Strom, later renamed Stromgarde. The Arathi formed an alliance with the High Elves of the far north after they aided them in a war against the Amani Empire of trolls.

[edit] Gnomes

The Gnomes are a small and ingenious race with magic and engineering proficiencies who were first introduced in Warcraft II: Tides of Darkness. They resided in Gnomeregan, an underground city with advanced technology, until they were driven out by a primitive race known as Troggs. Subsequent attempts by the Gnomish government to drive out the troggs included flooding the city with radiation which ultimately killed as many gnomes as troggs. In the end over eighty percent of the Gnomish race died. Refugees were taken in by the Dwarven capital of Ironforge, where they have been plotting revenge on the Troggs ever since. Gnomes have a notorious rivalry with the goblins, each thinking that the other takes the wrong attitude towards engineering. Gnomish engineering consists of cog and gear based machinery involving everything from robotic companions to large underground tram-systems, such as the Deeprun Tram, and flying machines, whereas Goblin engineering consists of explosion based tools and machines, like dynamite and zeppelins.

[edit] Night Elves

The Night Elves are one of the oldest races on Azeroth. More than ten thousand years ago a tribe of humanoids settled on the shores of the Well of Eternity. The Well's influence changed them fundamentally, but most importantly gave them the ability to use magic. After many years a schism occurred between the so-called Highborne, who were supported by the queen and were addicted to magic, and the rest of the population. An elf named Malfurion then discovered that the corrupted titan Sargeras and his Burning Legion were using the Well to enter into the world, with the intention of destroying it. Malfurion, his lover Tyrande, and the demigod Cenarius raced to the Well to try and destroy it. After a battle with the Highborne forces, they succeeded. The cataclysm not only destroyed the Well, but also most of the rest of the continent, resulting in a vast ocean separating the continents today.

The remainder of the Highborne were exiled, and sailed over the sea to Lordaeron where they named themselves High Elves. Later, it was discovered that Malfurion's brother Illidan managed to create a second Well of Eternity, so to stop another disaster a massive World Tree, Nordrassil, was planted over it. It gave the night elves several new abilities, for instance making them immortal. For the next ten thousand years, the survivors lived peacefully, until the second invasion of the Burning Legion. The races of Azeroth, both Horde and Alliance fought the Legion at the peak of Hyjal, until the elves managed to unleash the primal fury of Nordrassil killing the demon lord Archimonde and defeating the Burning Legion. Since then, the night elves have lost many of their abilities, and have planted a new World Tree called Teldrassil to try and recover them.

Night elves (once called Kaldorei) are imposing in stature, males being on average 7 feet tall. Male night elves are very muscular, with broad chests and shoulders, indicative of the strength that lies within both their minds and bodies. Female night elves are lithe and curvaceous, yet still muscular and strong. The race’s prominent eyebrows, long pointed ears and natural aspects imply a feral grace. Skin tones vary from purple, pink, blue or pale whitish-blue and their hair ranges in color from bright white to woodland green to a solid purple.

[edit] Dwarves

Born from the Earthen, original creations of the Titans, Dwarves are a short and strong race. The playable clan of dwarves reside in the mountain city of Ironforge in the Eastern Kingdoms continent. Their skin color can be from a charcoal-grey to a human tan.

The stoic dwarves of Ironforge are an ancient race of robust humanoids who live beneath the snow-capped mountains of Khaz Modan. The Dwarves have always been fast allies with the Humans, and they revel in the prospects of battle and storytelling alike. In past ages, the Dwarves rarely left the safety of their mountain fortresses. However, whenever the call to battle sounded, they rose up to defend their friends and allies with unmatched courage and valor. Dwarves have also engineered firearms.

Originally a race of miners, they have recently changed their focus to archeology. Due to a recent discovery that uncovered fragments of their ancient origins, the Dwarves have undergone a remarkable transformation. The discovery convinced the Dwarves that the mighty Titans created them from stone when the world was young. They feel that their destiny is now to search the world over for more signs and proof of their enchanted heritage and to rediscover the Titans' hidden legacies. To this end, the Dwarves have sent out their Prospectors to all ends of the world in the hopes of discovering new insight into their shrouded past. These journeys led to Dwarven excavation sites all over the known world, some of which serve as outposts and others as potential hunting grounds for enemies of the Dwarven race.

[edit] Draenei

Draenei are the last of the original Eredar, the race that eventually became corrupted by the evil Burning Legion. They greatly respect the Alliance's devout reverence for the Holy Light. Draenei have skin ranging from purple to pale blue, and both genders are relatively tall compared to humans, have cloven, goat-like hooves, and tails that resemble those of a lizard. Males usually have tentacle-like appendages extending from their chin, and occasionally large, complex structures on their forehead, while females have two horns on their temples extending backwards and thinner versions of the male's appendages hanging from behind the back of the jaw. The Draenei's leader was the prophet, Velen, who ruled with Archimonde and Kil'jaeden as the exarchs over Argus, the Draenei's original home world. Velen was contacted by the Naaru, who escorted him (and the Eredar who rejected Sargeras's offer of great power to the Eredar in exchange for their loyalty), across the cosmos, in the Naaru's dimensional traveling vessel, Tempest Keep. Kil'jaeden has hunted the Draenei since they left Argus with the Naaru. Some of the Draenei have succumbed to the Burning Legion's corruption, in body but not in mind, becoming the broken and lost ones, who were separated from the Light by the Legion's corruption. For example, one band of Draenei, led by Akama, were changed in appearance. Draenei range from 7 feet to 7 1/2 feet in height. While living in the world of Draenor, some had embraced the powers of the elements, becoming shaman. This practice was revealed to the Draenei farseer, Nobundo, by the spirit of the wind, which also uncovered that this would allow the light-forsaken Broken to still serve the Holy Light.

[edit] Horde

[edit] Orcs

The Orcs are generally green skinned and muscular humanoids. They are warlike, but formerly light brown shamanistic creatures from the planet Draenor. When the Burning Legion discovered that the Draenei were hiding on Draenor, they corrupted the Orcs and nearly wiped out the exiled race. The Orcs were then used as the Legion's primary war-machine in an attempt to invade and destroy Azeroth, through a device known as the Dark Portal. There, they were successful in their campaign against the Kingdom of Stormwind, but were eventually driven back through the Dark Portal and defeated.

Upon their defeat, the orcs that remained on Azeroth were rounded up and put into internment camps. Separation from the Burning Legion eventually caused lethargy in the orcs and their bloodlust faded after a few years. It was at this time that Thrall managed to escape his captivity at Durnholde Keep and free many of his captured bretheren, including Grom Hellscream of the Warsong Clan. The newly reformed Horde then fled to Kalimdor, where they met and befriended the Taurens.

The Orcs were eventually led into Night Elf territory and fought several skirmishes against them as they attempted to set up camps. Here, the Pit Lord Mannoroth returned and tempted Grom Hellscream into drinking from corrupted waters, placing the Warsong Clan back under the corruption of the Burning Legion. Grom then led his clan on a warpath through Night Elf lands and slaughtered the demi-god Cenarius. However, Grom was eventually freed and atoned for his deeds by aiding Thrall in defeating Pit Lord Mannoroth, sacrificing himself in the process and liberating the Orcs from their blood pact.

The liberated Orcs set aside their differences with the Night Elves and Humans to help defeat Archimonde at the Battle for Hyjal Summit. The Orcs then set out to carve a place for themselves on Azeroth in Kalimdor. They called their new homeland Durotar, after Thrall's father, Durotan. Their capital city was named Orgrimmar, after Orgrim Doomhammer, the former Warchief.

As of the present time, the following Orcish Clans survive within the Horde under Thrall:

  * The Frostwolf Clan
  * The Warsong Clan
  * The Bleeding Hollow Clan
  * The Shattered Hand Clan

These orc clans are merely examples of the very few numbers of Orcs who hold strong to their old shamanistic beliefs and clansmenship. Almost all the original clans are divided among the different Hordes (the Fel Horde in Outland and the Blackrock Clan in Blackrock Mountain both consider themselves to be the "True Horde"). However almost all Frostwolves, Warsong and Bleeding Hollow orcs are in the New Horde, ruled by Thrall. All other orcs in the New Horde have given up their clan affiliations; apart from a few Shattered Hand orcs, who make up the Assassins of the New Horde. However, most Shattered Hand orcs belong to the Fel Horde in Outland ruled by Kargath Bladefist.

[edit] Forsaken

The Forsaken were once Humans and Elves, but are now undead because of the plague brought by the Scourge. They control the western parts of the former Human kingdom of Lordaeron. They are led by the banshee queen, Sylvanas Windrunner in the catacombs beneath the ruined capital of Lordaeron, dubbed the "Undercity".

The Forsaken were part of the undead Scourge, but due to the intense magics used against the Lich King by Illidan Stormrage, they broke free of mind control. The undeath has actually provided benefits, in that their soldiers, Deathguards, can march for days disguised as ill Human soldiers, and bury themselves for shocking ambushes. The Forsaken are said to care little about the Horde; however, they seem to show sympathy for the blood elves. Their ultimate goal is establishing a place for themselves in a world that hates them, and creating a plague capable of wiping out the undead Scourge; they will wipe out anyone who stands in their way. They harbor no allegiance to their former allies, and vice versa. The Forsaken's alliance with the Horde is one of mere convenience.[1]

[edit] Tauren

The Tauren are one of the oldest races in Azeroth, a proud and tenacious race with bull-like features and a culture that is very similar to an evolved North American Indian culture. They are druidic, shamanistic, peaceful, and powerful beings. They have large hooves, three fingered hands, and a towering body structure. The Tauren reside in the grasslands of Mulgore.

Mulgore was fought over by the defending Tauren and the raiding Centaurs. The Tauren would have lost their land, but Thrall and his Orc brethren helped the peaceful Tauren after befriending their leader, Cairne Bloodhoof. The Tauren were honour-bound and they allied with the Horde. Cairne built an astounding, towering city, known as Thunder Bluff, on top of four great mesas where many different trades come together.

[edit] Blood Elves

After being exiled from Kalimdor, the High Elves sailed to the east and settled in the northern part of the continent. Their peace was to be short-lived, however, as the Amani Troll Tribe was not keen on having their lands settled by these newcomers. In order to defeat the Trolls, the Elves made a deal with the human Kingdom of Arathor: the Elves would agree to teach magic to the Humans in return for their aid. Upon victory, the High Elves solidified their dominion over the forests of Quel'thalas and founded a mighty capital.

During the second war, the Elves honored their treaty with the Humans and assisted in the defeat of the Horde. They also helped the Alliance in the third war as priests and sorcerers, but tragedy was soon to befall them...

During the third war, the Undead Scourge destroyed the High Elf capital and the source of their power, the Sunwell, along with the majority of their population. The remaining High Elves split into 2 factions - some kept their original heritage, but most followed Prince Kael'thas Sunstrider and began calling themselves Sin'dorei (which in their tongue means "children of the blood" - more commonly referred to as "Blood Elves") in homage to their loss. With the leadership of their prince the Blood Elves continue to defend their homeland from the terror of the Scourge. In their continued struggles on Azeroth, Kael'thas met the Naga, led by Lady Vashj, and accepted her help in protecting his people. This led to much suspicion from the Humans for whom Kael'thas was stationed under, and the Blood Elves fled with Lady Vashj to Outland to rendezvous with the exiled Illidan Stormrage. Kael'Thas later betrayed Illidan and began seeking power on his own, forming an alliance with the Burning Legion. Cheating his death in Tempest Keep, he later returned to the Isle of Quel'danas and re-ignited the Sunwell, where he seeks to summon Kil'Jaeden to Azeroth.

The Elves who remained in Eversong Forest have renounced their allegiance to Kael'thas and are now led by Lor'themar Theron. The Alliance mistrusts the Blood Elves and their lust for a source of magic, so the race has aligned with the Horde for the mutual benefit of reaching Outland.

[edit] Trolls

The Trolls of the Warcraft Universe have a vast and very diverse background with many different tribes, of which only the Darkspear are playable. The four major troll ethnicities include Forest, Jungle, Ice, and Sand. Other notable mentions include Dark trolls, about which very little is known, Zanzil the Outcast and his Followers, and the earliest of all trolls - the Zandalar tribe; from which all other trolls are said to have descended. Inside each of the four ethnicities, trolls are further divided into separate tribes with various allegiances.

During the second war, the Forest Trolls of Lordaeron allied with the Horde to help combat their ancient enemies, the High Elves, who had aligned with the Alliance. This alliance dissipated upon defeat of the Horde and internment of the remaining Orc clans.

The playable trolls, the Darkspear, are led by Vol'jin and fled the continent after splitting off from the Gurubashi (Jungle) Empire. When Thrall and his orc forces left the Eastern Kingdoms to sail to Kalimdor they crashed on an island near the centre of the ocean where they were met by the troll Sen'jin. Sen'jin, Thrall, and several other orcs and trolls were captured by murlocs soon after their arrival. Thrall managed to break from his cell and free many, but Sen'jin was sacrificed by a murloc sorcerer. It was in Sen'jin's honor that the Darkspear were allowed into the Horde.

[edit] Media set in the Warcraft universe

[edit] Computer games

  * Warcraft: Orcs & Humans (1994) - real-time strategy game
  * Warcraft II: Tides of Darkness (1995)
        o Warcraft II: Beyond the Dark Portal (1996) - expansion pack to Tides of Darkness
        o Warcraft II: Battle.net Edition (1999) - allowed online play of Warcraft II on Battle.net
  * Warcraft Adventures: Lord of the Clans - adventure game, cancelled
  * Warcraft III: Reign of Chaos (2002)
        o Warcraft III: The Frozen Throne (2003) - expansion pack to Reign of Chaos
  * World of Warcraft (2004) - MMORPG
        o World of Warcraft: The Burning Crusade (2007) - expansion pack to World of Warcraft
        o World of Warcraft: Wrath of the Lich King (2008) - second expansion to World of Warcraft

[edit] Tabletop games

  * Warcraft: The Board Game - strategic board game from Fantasy Flight Games, based heavily on Warcraft III
  * Warcraft: The Roleplaying Game - role-playing game from Sword & Sorcery
  * World of Warcraft: The Board Game - board game based on World of Warcraft, also by Fantasy Flight Games
  * World of Warcraft: The Adventure Game - board game based on World of Warcraft, also by Fantasy Flight Games
  * World of Warcraft Miniatures Game - an upcoming (November 2008) miniature war game based on World of Warcraft, by Upper Deck Entertainment.

[edit] Collectible card games

  * World of Warcraft Trading Card Game - 2006 [2]

[edit] Books

  * Warcraft: Day of the Dragon
  * Warcraft: Lord of the Clans
  * Warcraft: Of Blood and Honor
  * Warcraft: The Last Guardian
  * Warcraft: War of the Ancients Trilogy
  * World of Warcraft: Cycle of Hatred
  * World of Warcraft: Rise of the Horde
  * World of Warcraft: Tides of Darkness
  * World of Warcraft: Beyond the Dark Portal
  * Warcraft: Anthology Vol. 1

[edit] Film adaptation

In May 2006, production company Legendary Pictures acquired film rights to adapt Warcraft for the big screen with the game's publisher, Blizzard Entertainment. Blizzard had originally considered hiring a scribe for the film adaptation before teaming up with Legendary Pictures.[3] The companies plan to create a film that would not follow one specific Warcraft games' storyline, but would still take place in the fantasy universe.[4] According to Blizzard's Chief Operating Officer Paul Sams, the film's budget would be over $100 million.[5]

In June 2007, Legendary Pictures chairman Thomas Tull said that the studio was working closely with Blizzard's designers and writers to adapt World of Warcraft. Tull explained the desire to have a good story for the film adaptation, "I think some of the stuff that makes a game translate well... if there's a lore, if there's a road and story and a world that's been created, and characters that are interesting in a way that's more than just point and shoot."[6] World of Warcraft's lead designer Rob Pardo expressed interest in being able to adapt the intellectual property of World of Warcraft to the appropriate medium of the film. He also added that the designers were collaborating with Legendary Pictures on story and script development.[7]

In August 2007, at BlizzCon, it was unveiled that the film will aim for a projected 2009 release. It was also revealed that the movie will take place from an Alliance perspective and will be geared towards a PG-13 audience, with a storyline set one year before the beginning of the World of Warcraft storyline. Also revealed was the 100 million dollar budget. As of this time no director or cast are yet associated with its development. Thomas Tull stated that, "It’s not so much a quest movie. It’s more of a war movie."[8]

In a 2007 interview about directors, a Blizzard official stated they were "looking for someone along the lines of a Zack Snyder, Christopher Nolan type." As of 2008, no director has been announced.

TVG caught up with Blizzard Entertainment co-founder and vice president, Frank Pearce, at the Game Convention and asked about the current status of the feature film. He replied briefly:

"I think they're looking to assign a screenwriter and director to it right now...it's still really early." ( http://www.totalvideogames.com/news/Warcraft_Movie_Latest_13698_6933_0.htm )

[edit] Comics

A number of comic adaptations have been made including:

  * Warcraft: The Sunwell Trilogy is a manga series published by Tokyopop
  * World of Warcraft, the current ongoing series published by DC Comics imprint Wildstorm. [9] [10]

[edit] References

 1. ^ World Of Warcraft - Undead Race Page
 2. ^ October 25 Release Date - World of Warcraft Trading Card Game Blog
 3. ^ Pamela McClintock; Ben Fritz (2006-05-08). "Brave new 'World'", Variety. Retrieved on 2007-01-31. 
 4. ^ Borys Kit (2006-05-09). "Legendary enters world of 'Warcraft'", The Hollywood Reporter. Retrieved on 2007-01-31. 
 5. ^ Tal Blevins (2006-08-24). "GC 2006: Warcraft Movie Update", IGN. Retrieved on 2007-01-31. 
 6. ^ Brandon Sheffield; Brandon Boyer (2007-06-29). "H&G: Tull Talks World of Warcraft Film", GamaSutra.com. Retrieved on 2007-07-06. 
 7. ^ Brandon Sheffield; Jolene Spry (2007-06-28). "H&G: Blizzard's Pardo Talks WoW Film", GamaSutra.com. Retrieved on 2007-07-06. 
 8. ^ Paul Hayes (2007-08-05). "Warcraft Movie Chronicles: 'WoW' Film at BlizzCon 2007", Movie Chronicles. Retrieved on 2007-08-05. 
 9. ^ DC Comics World of Warcraft page
10. ^ Walter Simonson: Into The World Of Warcraft, Newsarama, November 25, 2007

[edit] External links

  * The History of Warcraft
  * Warcraft series official webpage
  * Warcraft universe at WoWWiki, a Warcraft wiki
  * An interview with Blizzard VP of Creative Development Chris Metzen on making Warcraft games and the creative process

[show] v • d • e The Warcraft series and related topics Games Warcraft: Orcs & Humans · II: Tides of Darkness (Beyond the Dark Portal) · Adventures: Lord of the Clans · III: Reign of Chaos (The Frozen Throne) · World of Warcraft (The Burning Crusade · Wrath of the Lich King) Books Day of the Dragon · Lord of the Clans · Of Blood and Honor · The Last Guardian · War of the Ancients Trilogy · The Sunwell Trilogy · Cycle of Hatred · Rise of the Horde · Tides of Darkness Professional Competition 2006 e-Sports World Champions · Korean WarCraft III Championships · Korean WarCraft III Rankings · Warcraft III World Championships Other Defense of the Ancients · JASS · MPQ (file format) · BLP (file format) [show] v • d • e Blizzard Entertainment and related topics Diablo series Diablo · Diablo II · Lord of Destruction · Diablo III StarCraft series StarCraft · Brood War · StarCraft: Ghost · StarCraft II Warcraft series Warcraft: Orcs & Humans · II: Tides of Darkness · Beyond the Dark Portal · III: Reign of Chaos · The Frozen Throne World of Warcraft · The Burning Crusade · Wrath of the Lich King Warcraft Adventures: Lord of the Clans Other titles Blackthorne · The Death and Return of Superman · Justice League Task Force · The Lost Vikings · Rock N' Roll Racing · RPM Racing People Allen Adham · Tom Chilton · Shahram Dabiri · Samwise Didier · Frank Pearce · Jeffrey Kaplan · Chris Metzen · Michael Morhaime · Rob Pardo Miscellaneous Activision Blizzard · Battle.net · Blizzard North · BlizzCon · Swingin' Ape Studios Retrieved from "http://en.wikipedia.org/wiki/Warcraft_(series)" Categories: Video game franchises • Warcraft • Blizzard games • Blizzard Entertainment media Hidden categories: Articles needing additional references from December 2007 • Articles that need to differentiate between fact and fiction Views

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Proteins are large organic compounds made of amino acids arranged in a linear chain and joined together by peptide bonds between the carboxyl and amino groups of adjacent amino acid residues. The sequence of amino acids in a protein is defined by a gene and encoded in the genetic code. Although this genetic code specifies 20 "standard" amino acids plus selenocysteine and - in certain archaea - pyrrolysine, the residues in a protein are sometimes chemically altered in post-translational modification. This can happen either before the protein is used in the cell, or as part of control mechanisms. Proteins can also work together to achieve a particular function, and they often associate to form stable complexes.

Like other biological macromolecules such as polysaccharides and nucleic acids, proteins are essential parts of organisms and participate in every process within cells. Many proteins are enzymes that catalyze biochemical reactions and are vital to metabolism. Proteins also have structural or mechanical functions, such as actin and myosin in muscle and the proteins in the cytoskeleton, which form a system of scaffolding that maintains cell shape. Other proteins are important in cell signaling, immune responses, cell adhesion, and the cell cycle. Proteins are also necessary in animals' diets, since animals cannot synthesize all the amino acids they need and must obtain essential amino acids from food. Through the process of digestion, animals break down ingested protein into free amino acids that are then used in metabolism.

The word protein comes from the Greek word πρώτειος (proteios) "primary". Proteins were first described and named by the Swedish chemist Jöns Jakob Berzelius in 1838. However, the central role of proteins in living organisms was not fully appreciated until 1926, when James B. Sumner showed that the enzyme urease was a protein. The first protein to be sequenced was insulin, by Frederick Sanger, who won the Nobel Prize for this achievement in 1958. The first protein structures to be solved included hemoglobin and myoglobin, by Max Perutz and Sir John Cowdery Kendrew, respectively, in 1958. The three-dimensional structures of both proteins were first determined by x-ray diffraction analysis; Perutz and Kendrew shared the 1962 Nobel Prize in Chemistry for these discoveries.

Biochemistry

Main articles: Amino acid and peptide bond

Resonance structures of the peptide bond that links individual amino acids to form a protein polymer.

Section of a protein structure showing serine and alanine residues linked together by peptide bonds. Carbons are shown in white and hydrogens are omitted for clarity.

Proteins are linear polymers built from 20 different L-α-amino acids. All amino acids possess common structural features, including an α carbon to which an amino group, a carboxyl group, and a variable side chain are bonded. Only proline differs from this basic structure as it contains an unusual ring to the N-end amine group, which forces the CO–NH amide moiety into a fixed conformation. The side chains of the standard amino acids, detailed in the list of standard amino acids, have different chemical properties that produce three-dimensional protein structure and are therefore critical to protein function. The amino acids in a polypeptide chain are linked by peptide bonds formed in a dehydration reaction. Once linked in the protein chain, an individual amino acid is called a residue, and the linked series of carbon, nitrogen, and oxygen atoms are known as the main chain or protein backbone. The peptide bond has two resonance forms that contribute some double-bond character and inhibit rotation around its axis, so that the alpha carbons are roughly coplanar. The other two dihedral angles in the peptide bond determine the local shape assumed by the protein backbone.

Due to the chemical structure of the individual amino acids, the protein chain has directionality. The end of the protein with a free carboxyl group is known as the C-terminus or carboxy terminus, whereas the end with a free amino group is known as the N-terminus or amino terminus.

The words protein, polypeptide, and peptide are a little ambiguous and can overlap in meaning. Protein is generally used to refer to the complete biological molecule in a stable conformation, whereas peptide is generally reserved for a short amino acid oligomers often lacking a stable three-dimensional structure. However, the boundary between the two is not well defined and usually lies near 20–30 residues. Polypeptide can refer to any single linear chain of amino acids, usually regardless of length, but often implies an absence of a defined conformation.

Synthesis

Main article: Protein biosynthesis

The DNA sequence of a gene encodes the amino acid sequence of a protein.

Proteins are assembled from amino acids using information encoded in genes. Each protein has its own unique amino acid sequence that is specified by the nucleotide sequence of the gene encoding this protein. The genetic code is a set of three-nucleotide sets called codons and each three-nucleotide combination stands for an amino acid, for example AUG stands for methionine. Because DNA contains four nucleotides, the total number of possible codons is 64; hence, there is some redundancy in the genetic code, with some amino acids specified by more than one codon. Genes encoded in DNA are first transcribed into pre-messenger RNA (mRNA) by proteins such as RNA polymerase. Most organisms then process the pre-mRNA (also known as a primary transcript) using various forms of post-transcriptional modification to form the mature mRNA, which is then used as a template for protein synthesis by the ribosome. In prokaryotes the mRNA may either be used as soon as it is produced, or be bound by a ribosome after having moved away from the nucleoid. In contrast, eukaryotes make mRNA in the cell nucleus and then translocate it across the nuclear membrane into the cytoplasm, where protein synthesis then takes place. The rate of protein synthesis is higher in prokaryotes than eukaryotes and can reach up to 20 amino acids per second.

The process of synthesizing a protein from an mRNA template is known as translation. The mRNA is loaded onto the ribosome and is read three nucleotides at a time by matching each codon to its base pairing anticodon located on a transfer RNA molecule, which carries the amino acid corresponding to the codon it recognizes. The enzyme aminoacyl tRNA synthetase "charges" the tRNA molecules with the correct amino acids. The growing polypeptide is often termed the nascent chain. Proteins are always biosynthesized from N-terminus to C-terminus.

The size of a synthesized protein can be measured by the number of amino acids it contains and by its total molecular mass, which is normally reported in units of daltons (synonymous with atomic mass units), or the derivative unit kilodalton (kDa). Yeast proteins are on average 466 amino acids long and 53 kDa in mass. The largest known proteins are the titins, a component of the muscle sarcomere, with a molecular mass of almost 3,000 kDa and a total length of almost 27,000 amino acids.

Chemical synthesis

Short proteins can also be synthesized chemically by a family of methods known as peptide synthesis, which rely on organic synthesis techniques such as chemical ligation to produce peptides in high yield. Chemical synthesis allows for the introduction of non-natural amino acids into polypeptide chains, such as attachment of fluorescent probes to amino acid side chains. These methods are useful in laboratory biochemistry and cell biology, though generally not for commercial applications. Chemical synthesis is inefficient for polypeptides longer than about 300 amino acids, and the synthesized proteins may not readily assume their native tertiary structure. Most chemical synthesis methods proceed from C-terminus to N-terminus, opposite the biological reaction.

Structure of proteins

Main article: Protein structure

Three possible representations of the three-dimensional structure of the protein triose phosphate isomerase. Left: all-atom representation colored by atom type. Middle: simplified representation illustrating the backbone conformation, colored by secondary structure. Right: Solvent-accessible surface representation colored by residue type (acidic residues red, basic residues blue, polar residues green, nonpolar residues white).

Most proteins fold into unique 3-dimensional structures. The shape into which a protein naturally folds is known as its native state. Although many proteins can fold unassisted, simply through the chemical properties of their amino acids, others require the aid of molecular chaperones to fold into their native states. Biochemists often refer to four distinct aspects of a protein's structure:

• Primary structure: the amino acid sequence
• Secondary structure: regularly repeating local structures stabilized by hydrogen bonds. The most common examples are the alpha helix and beta sheet. Because secondary structures are local, many regions of different secondary structure can be present in the same protein molecule.
• Tertiary structure: the overall shape of a single protein molecule; the spatial relationship of the secondary structures to one another. Tertiary structure is generally stabilized by nonlocal interactions, most commonly the formation of a hydrophobic core, but also through salt bridges, hydrogen bonds, disulfide bonds, and even post-translational modifications. The term "tertiary structure" is often used as synonymous with the term fold.
• Quaternary structure: the shape or structure that results from the interaction of more than one protein molecule, usually called protein subunits in this context, which function as part of the larger assembly or protein complex.

NMR structures of the protein cytochrome c in solution show the constantly shifting dynamic structure of the protein. Larger version.

Proteins are not entirely rigid molecules. In addition to these levels of structure, proteins may shift between several related structures while they perform their functions. In the context of these functional rearrangements, these tertiary or quaternary structures are usually referred to as "conformations", and transitions between them are called conformational changes. Such changes are often induced by the binding of a substrate molecule to an enzyme's active site, or the physical region of the protein that participates in chemical catalysis. In solution all proteins also undergo variation in structure through thermal vibration and the collision with other molecules, see the animation on the right.

Molecular surface of several proteins showing their comparative sizes. From left to right are: immunoglobulin G (IgG, an antibody), hemoglobin, insulin (a hormone), adenylate kinase (an enzyme), and glutamine synthetase (an enzyme).

Proteins can be informally divided into three main classes, which correlate with typical tertiary structures: globular proteins, fibrous proteins, and membrane proteins. Almost all globular proteins are soluble and many are enzymes. Fibrous proteins are often structural; membrane proteins often serve as receptors or provide channels for polar or charged molecules to pass through the cell membrane.

A special case of intramolecular hydrogen bonds within proteins, poorly shielded from water attack and hence promoting their own dehydration, are called dehydrons.

Structure determination

Discovering the tertiary structure of a protein, or the quaternary structure of its complexes, can provide important clues about how the protein performs its function. Common experimental methods of structure determination include X-ray crystallography and NMR spectroscopy, both of which can produce information at atomic resolution. Cryoelectron microscopy is used to produce lower-resolution structural information about very large protein complexes, including assembled viruses; a variant known as electron crystallography can also produce high-resolution information in some cases, especially for two-dimensional crystals of membrane proteins. Solved structures are usually deposited in the Protein Data Bank (PDB), a freely available resource from which structural data about thousands of proteins can be obtained in the form of Cartesian coordinates for each atom in the protein.

Many more gene sequences are known than protein structures. Further, the set of solved structures is biased toward proteins that can be easily subjected to the conditions required in X-ray crystallography, one of the major structure determination methods. In particular, globular proteins are comparatively easy to crystallize in preparation for X-ray crystallography. Membrane proteins, by contrast, are difficult to crystallize and are underrepresented in the PDB. Structural genomics initiatives have attempted to remedy these deficiencies by systematically solving representative structures of major fold classes. Protein structure prediction methods attempt to provide a means of generating a plausible structure for proteins whose structures have not been experimentally determined.

Cellular functions

Proteins are the chief actors within the cell, said to be carrying out the duties specified by the information encoded in genes. With the exception of certain types of RNA, most other biological molecules are relatively inert elements upon which proteins act. Proteins make up half the dry weight of an Escherichia coli cell, whereas other macromolecules such as DNA and RNA make up only 3% and 20%, respectively. The set of proteins expressed in a particular cell or cell type is known as its proteome.

The enzyme hexokinase is shown as a simple ball-and-stick molecular model. To scale in the top right-hand corner are two of its substrates, ATP and glucose.

The chief characteristic of proteins that allows their diverse set of functions is their ability to bind other molecules specifically and tightly. The region of the protein responsible for binding another molecule is known as the binding site and is often a depression or "pocket" on the molecular surface. This binding ability is mediated by the tertiary structure of the protein, which defines the binding site pocket, and by the chemical properties of the surrounding amino acids' side chains. Protein binding can be extraordinarily tight and specific; for example, the ribonuclease inhibitor protein binds to human angiogenin with a sub-femtomolar dissociation constant (<10^-15 M) but does not bind at all to its amphibian homolog onconase (>1 M). Extremely minor chemical changes such as the addition of a single methyl group to a binding partner can sometimes suffice to nearly eliminate binding; for example, the aminoacyl tRNA synthetase specific to the amino acid valine discriminates against the very similar side chain of the amino acid isoleucine.

Proteins can bind to other proteins as well as to small-molecule substrates. When proteins bind specifically to other copies of the same molecule, they can oligomerize to form fibrils; this process occurs often in structural proteins that consist of globular monomers that self-associate to form rigid fibers. Protein-protein interactions also regulate enzymatic activity, control progression through the cell cycle, and allow the assembly of large protein complexes that carry out many closely related reactions with a common biological function. Proteins can also bind to, or even be integrated into, cell membranes. The ability of binding partners to induce conformational changes in proteins allows the construction of enormously complex signaling networks.

Enzymes

Main article: Enzyme

The best-known role of proteins in the cell is as enzymes, which catalyze chemical reactions. Enzymes are usually highly specific and accelerate only one or a few chemical reactions. Enzymes carry out most of the reactions involved in metabolism, as well as manipulating DNA in processes such as DNA replication, DNA repair, and transcription. Some enzymes act on other proteins to add or remove chemical groups in a process known as post-translational modification. About 4,000 reactions are known to be catalyzed by enzymes. The rate acceleration conferred by enzymatic catalysis is often enormous - as much as 10¹⁷-fold increase in rate over the uncatalyzed reaction in the case of orotate decarboxylase (78 million years without the enzyme, 18 milliseconds with the enzyme).

The molecules bound and acted upon by enzymes are called substrates. Although enzymes can consist of hundreds of amino acids, it is usually only a small fraction of the residues that come in contact with the substrate, and an even smaller fraction - 3-4 residues on average - that are directly involved in catalysis. The region of the enzyme that binds the substrate and contains the catalytic residues is known as the active site.

Cell signaling and ligand transport

A mouse antibody against cholera that binds a carbohydrate antigen.

Many proteins are involved in the process of cell signaling and signal transduction. Some proteins, such as insulin, are extracellular proteins that transmit a signal from the cell in which they were synthesized to other cells in distant tissues. Others are membrane proteins that act as receptors whose main function is to bind a signaling molecule and induce a biochemical response in the cell. Many receptors have a binding site exposed on the cell surface and an effector domain within the cell, which may have enzymatic activity or may undergo a conformational change detected by other proteins within the cell.

Antibodies are protein components of adaptive immune system whose main function is to bind antigens, or foreign substances in the body, and target them for destruction. Antibodies can be secreted into the extracellular environment or anchored in the membranes of specialized B cells known as plasma cells. Whereas enzymes are limited in their binding affinity for their substrates by the necessity of conducting their reaction, antibodies have no such constraints. An antibody's binding affinity to its target is extraordinarily high.

Many ligand transport proteins bind particular small biomolecules and transport them to other locations in the body of a multicellular organism. These proteins must have a high binding affinity when their ligand is present in high concentrations, but must also release the ligand when it is present at low concentrations in the target tissues. The canonical example of a ligand-binding protein is haemoglobin, which transports oxygen from the lungs to other organs and tissues in all vertebrates and has close homologs in every biological kingdom.

Transmembrane proteins can also serve as ligand transport proteins that alter the permeability of the cell membrane to small molecules and ions. The membrane alone has a hydrophobic core through which polar or charged molecules cannot diffuse. Membrane proteins contain internal channels that allow such molecules to enter and exit the cell. Many ion channel proteins are specialized to select for only a particular ion; for example, potassium and sodium channels often discriminate for only one of the two ions.

Structural proteins

Structural proteins confer stiffness and rigidity to otherwise-fluid biological components. Most structural proteins are fibrous proteins; for example, actin and tubulin are globular and soluble as monomers, but polymerize to form long, stiff fibers that comprise the cytoskeleton, which allows the cell to maintain its shape and size. Collagen and elastin are critical components of connective tissue such as cartilage, and keratin is found in hard or filamentous structures such as hair, nails, feathers, hooves, and some animal shells.

Other proteins that serve structural functions are motor proteins such as myosin, kinesin, and dynein, which are capable of generating mechanical forces. These proteins are crucial for cellular motility of single celled organisms and the sperm of many sexually reproducing multicellular organisms. They also generate the forces exerted by contracting muscles.

Methods of study

Main article: Protein methods

As some of the most commonly studied biological molecules, the activities and structures of proteins are examined both in vitro and in vivo. In vitro studies of purified proteins in controlled environments are useful for learning how a protein carries out its function: for example, enzyme kinetics studies explore the chemical mechanism of an enzyme's catalytic activity and its relative affinity for various possible substrate molecules. By contrast, in vivo experiments on proteins' activities within cells or even within whole organisms can provide complementary information about where a protein functions and how it is regulated.

Protein purification

Main article: Protein purification

In order to perform in vitro analysis, a protein must be purified away from other cellular components. This process usually begins with cell lysis, in which a cell's membrane is disrupted and its internal contents released into a solution known as a crude lysate. The resulting mixture can be purified using ultracentrifugation, which fractionates the various cellular components into fractions containing soluble proteins; membrane lipids and proteins; cellular organelles, and nucleic acids. Precipitation by a method known as salting out can concentrate the proteins from this lysate. Various types of chromatography are then used to isolate the protein or proteins of interest based on properties such as molecular weight, net charge and binding affinity. The level of purification can be monitored using various types of gel electrophoresis if the desired protein's molecular weight and isoelectric point are known, by spectroscopy if the protein has distinguishable spectroscopic features, or by enzyme assays if the protein has enzymatic activity. Additionally, proteins can be isolated according their charge using electrofocusing.

For natural proteins, a series of purification steps may be necessary to obtain protein sufficiently pure for laboratory applications. To simplify this process, genetic engineering is often used to add chemical features to proteins that make them easier to purify without affecting their structure or activity. Here, a "tag" consisting of a specific amino acid sequence, often a series of histidine residues (a "His-tag"), is attached to one terminus of the protein. As a result, when the lysate is passed over a chromatography column containing nickel, the histidine residues ligate the nickel and attach to the column while the untagged components of the lysate pass unimpeded.

Cellular localization

Proteins in different cellular compartments and structures tagged with green fluorescent protein (here, white).

The study of proteins in vivo is often concerned with the synthesis and localization of the protein within the cell. Although many intracellular proteins are synthesized in the cytoplasm and membrane-bound or secreted proteins in the endoplasmic reticulum, the specifics of how proteins are targeted to specific organelles or cellular structures is often unclear. A useful technique for assessing cellular localization uses genetic engineering to express in a cell a fusion protein or chimera consisting of the natural protein of interest linked to a "reporter" such as green fluorescent protein (GFP). The fused protein's position within the cell can be cleanly and efficiently visualized using microscopy, as shown in the figure opposite. In these cases, additional fluorescent chimeric proteins are generally required to prove the inferred localization.

Other methods for elucidating the cellular location of proteins requires the use of known compartmental markers for regions such as the ER, the Golgi, lysosomes/vacuoles, mitochondria, chloroplasts, plasma membrane, etc. With the use of fluorescently-tagged versions of these markers or of antibodies to known markers, it becomes much simpler to identify the localization of a protein of interest. For example, indirect immunofluorescence will allow for fluorescence colocalization and demonstration of location. Fluorescent dyes are used to label cellular compartments for a similar purpose.

Other possibilities exist, as well. For example, immunohistochemistry usually utilizes an antibody to one or more proteins of interest that are conjugated to enzymes yielding either luminescent or chromogenic signals that can be compared between samples, allowing for localization information.

Another applicable technique is cofractionation in sucrose (or other material) gradients using isopycnic centrifugation. While this technique does not prove colocalization of a compartment of known density and the protein of interest, it does increase the likelihood, and is more amenable to large-scale studies.

Finally, the gold-standard method of cellular localization is immunoelectron microscopy. This technique also uses an antibody to the protein of interest, along with classical electron microscopy techniques. The sample is prepared for normal electron microscopic examination, and then treated with an antibody to the protein of interest that is conjugated to an extremely electro-dense material, usually gold. This allows for the localization of both ultrastructural details as well as the protein of interest.

Through another genetic engineering application known as site-directed mutagenesis, researchers can alter the protein sequence and hence its structure, cellular localization, and susceptibility to regulation, which can be followed in vivo by GFP tagging or in vitro by enzyme kinetics and binding studies.

Proteomics and bioinformatics

Main articles: Proteomics and Bioinformatics

The total complement of proteins present at a time in a cell or cell type is known as its proteome, and the study of such large-scale data sets defines the field of proteomics, named by analogy to the related field of genomics. Key experimental techniques in proteomics include 2D electrophoresis, which allows the separation of a large number of proteins, mass spectrometry, which allows rapid high-throughput identification of proteins and sequencing of peptides (most often after in-gel digestion), protein microarrays, which allow the detection of the relative levels of a large number of proteins present in a cell, and two-hybrid screening, which allows the systematic exploration of protein-protein interactions. The total complement of biologically possible such interactions is known as the interactome. A systematic attempt to determine the structures of proteins representing every possible fold is known as structural genomics.

The large amount of genomic and proteomic data available for a variety of organisms, including the human genome, allows researchers to efficiently identify homologous proteins in distantly related organisms by sequence alignment. Sequence profiling tools can perform more specific sequence manipulations such as restriction enzyme maps, open reading frame analyses for nucleotide sequences, and secondary structure prediction. From this data phylogenetic trees can be constructed and evolutionary hypotheses developed using special software like ClustalW regarding the ancestry of modern organisms and the genes they express. The field of bioinformatics seeks to assemble, annotate, and analyze genomic and proteomic data, applying computational techniques to biological problems such as gene finding and cladistics.

Structure prediction and simulation

Complementary to the field of structural genomics, protein structure prediction seeks to develop efficient ways to provide plausible models for proteins whose structures have not yet been determined experimentally. The most successful type of structure prediction, known as homology modeling, relies on the existence of a "template" structure with sequence similarity to the protein being modeled; structural genomics' goal is to provide sufficient representation in solved structures to model most of those that remain. Although producing accurate models remains a challenge when only distantly related template structures are available, it has been suggested that sequence alignment is the bottleneck in this process, as quite accurate models can be produced if a "perfect" sequence alignment is known. Many structure prediction methods have served to inform the emerging field of protein engineering, in which novel protein folds have already been designed. A more complex computational problem is the prediction of intermolecular interactions, such as in molecular docking and protein-protein interaction prediction.

The processes of protein folding and binding can be simulated using techniques derived from molecular dynamics, which increasingly take advantage of distributed computing as in the Folding@Home project. The folding of small alpha-helical protein domains such as the villin headpiece and the HIV accessory protein have been successfully simulated in silico, and hybrid methods that combine standard molecular dynamics with quantum mechanics calculations have allowed exploration of the electronic states of rhodopsins.

Nutrition

Further information: [[:Protein in nutrition]]

Most microorganisms and plants can biosynthesize all 20 standard amino acids, while animals, (including humans) must obtain some of the amino acids from the diet. Key enzymes in the biosynthetic pathways that synthesize certain amino acids - such as aspartokinase, which catalyzes the first step in the synthesis of lysine, methionine, and threonine from aspartate - are not present in animals. The amino acids that an organism cannot synthesize on its own are referred to as essential amino acids. If amino acids are present in the environment, microorganisms can conserve energy by taking up the amino acids from their surroundings and downregulating their biosynthetic pathways.

In animals, amino acids are obtained through the consumption of foods containing protein. Ingested proteins are broken down through digestion, which typically involves denaturation of the protein through exposure to acid and hydrolysis by enzymes called proteases. Some ingested amino acids are used for protein biosynthesis, while others are converted to glucose through gluconeogenesis, or fed into the citric acid cycle. This use of protein as a fuel is particularly important under starvation conditions as it allows the body's own proteins to be used to support life, particularly those found in muscle. Amino acids are also an important dietary source of nitrogen.

History

Further information: [[:History of molecular biology]]

Proteins were recognized as a distinct class of biological molecules in the eighteenth century by Antoine Fourcroy and others, distinguished by the molecules' ability to coagulate or flocculate under treatments with heat or acid. Noted examples at the time included albumin from egg whites, blood, serum albumin, fibrin, and wheat gluten. Dutch chemist Gerhardus Johannes Mulder carried out elemental analysis of common proteins and found that nearly all proteins had the same empirical formula. The term "protein" to describe these molecules was proposed in 1838 by Mulder's associate Jöns Jakob Berzelius. Mulder went on to identify the products of protein degradation such as the amino acid leucine for which he found a (nearly correct) molecular weight of 131 Da.

The difficulty in purifying proteins in large quantities made them very difficult for early protein biochemists to study. Hence, early studies focused on proteins that could be purified in large quantities, e.g., those of blood, egg white, various toxins, and digestive/metabolic enzymes obtained from slaughterhouses. In the late 1950s, the Armour Hot Dog Co. purified 1 kg (= one million milligrams) of pure bovine pancreatic ribonuclease A and made it freely available to scientists around the world.

Linus Pauling is credited with the successful prediction of regular protein secondary structures based on hydrogen bonding, an idea first put forth by William Astbury in 1933. Later work by Walter Kauzmann on denaturation, based partly on previous studies by Kaj Linderstrøm-Lang, contributed an understanding of protein folding and structure mediated by hydrophobic interactions. In 1949 Fred Sanger correctly determined the amino acid sequence of insulin, thus conclusively demonstrating that proteins consisted of linear polymers of amino acids rather than branched chains, colloids, or cyclols. The first atomic-resolution structures of proteins were solved by X-ray crystallography in the 1960s and by NMR in the 1980s. As of 2006, the Protein Data Bank has nearly 40,000 atomic-resolution structures of proteins. In more recent times, cryo-electron microscopy of large macromolecular assemblies and computational protein structure prediction of small protein domains are two methods approaching atomic resolution.

See also

• Comparative Toxicogenomics Database
• Amino acid
• Essential amino acid
• Protein design
• Isoelectric point
• Intein
• List of recombinant proteins
• List of proteins
• Prion
• Edible protein per unit area of land
• Expression cloning
• Proteopathy
• Software for protein modeling
• Proteopedia

External links

• Protein Songs (Stuart Mitchell - DNA Music Project), 'When a "tape" of mRNA passes through the "playing head" of a ribosome, the "notes" produced are amino acids and the pieces of music they make up are proteins.'
• Proteins (the journal), also called "Proteins: Structure, Function, and Bioinformatics" and previously "Proteins: Structure, Function, and Genetics" (1986–1995).

Databases and projects

• Comparative Toxicogenomics Database curates protein-chemical interactions, as well as gene/protein-disease relationships and chemical-disease relationships.
• Bioinformatic Harvester A Meta search engine (29 databases) for gene and protein information.
• The Protein Databank (see also PDB Molecule of the Month, presenting short accounts on selected proteins from the PDB)
• Proteopedia - Life in 3D: rotatable, zoomable 3D model with wiki annotations for every known protein molecular structure.
• UniProt the Universal Protein Resource
• Human Protein Atlas
• iHOP - Information Hyperlinked over Proteins
• MIT's Laboratory for Protein Molecular Self-Assembly
• NCBI Entrez Protein database
• NCBI Protein Structure database
• Human Protein Reference Database
• Human Proteinpedia
• Folding@Home (Stanford University)

Tutorials and educational websites

• Proteins: Biogenesis to Degradation - The Virtual Library of Biochemistry and Cell Biology
• Amino acid metabolism
• Data Book of Molecules - Home Page for Learning Environmental Chemistry