User:Cody Couperus/Sandbox 1

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<StructureSection load='1PPB' size='350' side='right' caption='Thrombin (1PPB) viewed in cartoon representation colored by secondary structure. Active site residues Ser195, Asp102, and His57 are viewed in ball and stick form.' scene='58/583418/Thombin_main_secondary/2'>
<StructureSection load='1PPB' size='350' side='right' caption='Thrombin (1PPB) viewed in cartoon representation colored by secondary structure. Active site residues Ser195, Asp102, and His57 are viewed in ball and stick form.' scene='58/583418/Thombin_main_secondary/2'>
==Introduction==
==Introduction==
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<scene name='58/583418/Thombin_main_secondary/2'>Thrombin</scene> is the serine protease that catalyzes the penultimate step in blood coagulation. It is activated from its zymogen, prothrombin, at the site of tissue injury by [[Factor_Xa | FXa]] and its cofactor FVa in the presence of phospholipid membrane and calcium. Thrombin is then able to catalyze the cleavage of [[Fibrinogen | fibrinogen]] to insoluable fibrin which spontaneously polymerizes to form a stable clot.<ref name="7023326">PMID: 7023326</ref><ref name="11001069">PMID: 11001069</ref> Thrombin also acts as a procoagulant by:
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<scene name='58/583418/Thombin_main_secondary/2'>Thrombin</scene> is the serine protease that catalyzes the penultimate step in blood coagulation. It is activated from its zymogen, prothrombin, at the site of tissue injury by [[Factor_Xa | FXa]] and its cofactor FVa in the presence of phospholipid membrane and calcium. Thrombin is then able to catalyze the cleavage of [[Fibrinogen | fibrinogen]] to insoluable fibrin which spontaneously polymerizes to form a stable clot.<ref name="7023326">PMID: 7023326</ref><ref name="one">PMID: 11001069</ref> Thrombin also acts as a procoagulant by:
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* Activating platelets through their protease activated receptors (PARs)<ref name="11001069"/>
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* Activating platelets through their protease activated receptors (PARs)<ref name="one"/>
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* Preventing VWF processing by cleaving ADAMTS13 <ref name="15388580">PMID: 15388580</ref><ref name="15994286">PMID: 15994286</ref>
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* Preventing VWF processing by cleaving ADAMTS13 <ref name="two">PMID: 15388580</ref><ref name="three">PMID: 15994286</ref>
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* Enhancing its own production through [[FIX]] activation <ref name="15994286"/>
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* Enhancing its own production through [[FIX]] activation <ref name="three"/>
* Activating the fibrin crosslinking transglutaminase [[Factor_XIII | FXIII]] <ref>PMID: 4811064</ref>
* Activating the fibrin crosslinking transglutaminase [[Factor_XIII | FXIII]] <ref>PMID: 4811064</ref>
* Activation of thrombin activatable fibrinolysis inhibitor (TAFI) <ref>PMID: 20229688</ref>
* Activation of thrombin activatable fibrinolysis inhibitor (TAFI) <ref>PMID: 20229688</ref>
Activity of thrombin is regulated physiologically by the serpin inhibitors:
Activity of thrombin is regulated physiologically by the serpin inhibitors:
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* [[Antithrombin]] <ref name="15994286"/><ref>PMID: 24477356</ref><ref>PMID: 23809129</ref>
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* [[Antithrombin]] <ref name="three"/><ref>PMID: 24477356</ref><ref>PMID: 23809129</ref>
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* Heparin cofactor II <ref name="15994286"/><ref>PMID: 24477356</ref><ref>PMID: 23809129</ref>
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* Heparin cofactor II <ref name="three"/><ref>PMID: 24477356</ref><ref>PMID: 23809129</ref>
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* Protein C inhibitor <ref name="15994286"/><ref>PMID: 24477356</ref><ref>PMID: 23809129</ref>
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* Protein C inhibitor <ref name="three"/><ref>PMID: 24477356</ref><ref>PMID: 23809129</ref>
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* Protease nexin 1 <ref name="15994286"/><ref>PMID: 24477356</ref><ref>PMID: 23809129</ref>
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* Protease nexin 1 <ref name="three"/><ref>PMID: 24477356</ref><ref>PMID: 23809129</ref>
Generation of thrombin is decreased when thrombin reaches endothelial lining and interacts with [[1fge |thrombomodulin]] which significantly increases activity of thrombin in activating protein C (APC).<ref>PMID: 3029867</ref> This enzyme will go on to inactivate FVa<ref>PMID: 7989361</ref><ref>PMID: 8639840</ref> and [[Factor_VIII | FVIIIa]]<ref>PMID: 8639840</ref> , cofactors for activation of prothrombin<ref>PMID: 15147718</ref> and [[Factor_Xa | FXa]]<ref>PMID: 10881749</ref>, respectively.
Generation of thrombin is decreased when thrombin reaches endothelial lining and interacts with [[1fge |thrombomodulin]] which significantly increases activity of thrombin in activating protein C (APC).<ref>PMID: 3029867</ref> This enzyme will go on to inactivate FVa<ref>PMID: 7989361</ref><ref>PMID: 8639840</ref> and [[Factor_VIII | FVIIIa]]<ref>PMID: 8639840</ref> , cofactors for activation of prothrombin<ref>PMID: 15147718</ref> and [[Factor_Xa | FXa]]<ref>PMID: 10881749</ref>, respectively.
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By balancing substrate specificity, activity, and inhibition thrombin plays a central role in the blood coagulation cascade. <ref name="15994286"/>
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By balancing substrate specificity, activity, and inhibition thrombin plays a central role in the blood coagulation cascade. <ref name="three"/>

Revision as of 14:59, 28 April 2014

Thrombin: Structure and Function

Thrombin (1PPB) viewed in cartoon representation colored by secondary structure. Active site residues Ser195, Asp102, and His57 are viewed in ball and stick form.

Drag the structure with the mouse to rotate

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Cody Couperus

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