Thrombin: Difference between revisions

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Michal Harel, Alexander Berchansky, Cody Couperus, Joel L. Sussman

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 <StructureSection load='1ppb' size='350' side='right' scene='' caption='Human thrombin large (red) and small (green) subunits complex with prolinamide derivative (PDB code [[1ppb]])'>
 ==Introduction==
-'''Thrombin''' (Thr) is a serine protease.  '''Prothrombin''' (PThr) is cleaved to form Thr in the coagulation cascade.  The first step of the cleavage is at residue R320 and produces '''meizothrombin''' (MThr). Thr catalyzes the conversion of fibrinogen to the insoluble fibrin.  Thr is composed of heavy chain (HC) and light chain (LC).  Prethrombin-1 lacks 155 N-terminal residues of PThr and is composed of a single polypeptide chain.  '''Prethrombin-2''' is the product of proteolysis of '''prethrombin-1''' by trypsin or by active factor X.  P-PACK Thr is a chemicaly modified Thr with inactivated catalytic site and active anion binding site.  Hirudin is the most potent natural inhibitor of Thr ([[Sean Swale/Human Thrombin Inhibitor]]).   For some more details see [[Serine Proteases]]. Prothrombin cleavage results in the creation of thrombin, a coagulative agent in plasma and is connected to fibrinolysis and platelet activation. During this process several peptides involved in the conversion are released into the plasma, and the remaining protein splits into two portions(http://www.uniprot.org/citations/3759958). It has been shown that prothrombin has a statistically significant connection to the occurrence of ischemic stroke with the presence of the G20210A mutation, though the cause was not isolated to prothrombin alone (http://www.uniprot.org/citations/15534175) (these links added by Connor Gramazio).  Some additional details in<br />
+'''Thrombin''' (Thr) is a serine protease.  '''Prothrombin''' (PThr) is cleaved to form Thr in the coagulation cascade.  The first step of the cleavage is at residue R320 and produces '''meizothrombin''' (MThr). Thr catalyzes the conversion of fibrinogen to the insoluble fibrin.  Thr is composed of heavy chain (HC) and light chain (LC).  Prethrombin-1 lacks 155 N-terminal residues of PThr and is composed of a single polypeptide chain.  '''Prethrombin-2''' is the product of proteolysis of '''prethrombin-1''' by trypsin or by active factor X.  P-PACK Thr is a chemically modified Thr with inactivated catalytic site and active anion binding site.  Hirudin is the most potent natural inhibitor of Thr ([[Sean Swale/Human Thrombin Inhibitor]]).   For some more details see [[Serine Proteases]]. Prothrombin cleavage results in the creation of thrombin, a coagulative agent in plasma and is connected to fibrinolysis and platelet activation. During this process several peptides involved in the conversion are released into the plasma, and the remaining protein splits into two portions(http://www.uniprot.org/citations/3759958). It has been shown that prothrombin has a statistically significant connection to the occurrence of ischemic stroke with the presence of the G20210A mutation, though the cause was not isolated to prothrombin alone (http://www.uniprot.org/citations/15534175) (these links added by Connor Gramazio).  Some additional details in<br />
 * [[Ann Taylor 115]]<br />
 * [[Sean Swale/Human Thrombin Inhibitor]]<br />
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 * [[Thrombin (hebrew)]]<br />
-<scene name='58/583418/Thombin_main_secondary/2'>Thrombin</scene> catalyzes the penultimate step in blood coagulation. It is activated from its [http://en.wikipedia.org/wiki/Zymogen zymogen], prothrombin, at the site of tissue injury by [[Factor_Xa | Factor Xa (FXa)]] and its cofactor [http://en.wikipedia.org/wiki/Factor_V 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="zero">PMID: 7023326</ref><ref name="one">PMID: 11001069</ref> Thrombin also acts as a procoagulant by:
+<scene name='58/583418/Thombin_main_secondary/2'>Thrombin</scene> catalyzes the penultimate step in blood coagulation. It is activated from its [http://en.wikipedia.org/wiki/Zymogen zymogen], prothrombin, at the site of tissue injury by [[Factor_Xa | Factor Xa (FXa)]] and its cofactor [http://en.wikipedia.org/wiki/Factor_V FVa] in the presence of phospholipid membrane and calcium. Thrombin is then able to catalyze the cleavage of [[Fibrinogen | fibrinogen]] to insoluble fibrin which spontaneously polymerizes to form a stable clot.<ref name="zero">PMID: 7023326</ref><ref name="one">PMID: 11001069</ref> Thrombin also acts as a procoagulant by:
 * Activating platelets through their [http://en.wikipedia.org/wiki/Protease-activated_receptor protease activated receptors (PARs)]<ref name="one"/>