User:Cody Couperus/Sandbox 1: Difference between revisions

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Prothrombin is the zymogen form of thrombin. From N-terminal to C-terminal it consists of a Gla domain, two kringle domains, and a catalytic domain. The Gla domain is formed by vitamin K dependent carboxylation of glutamate residues.<ref>PMID: 18374193</ref>

'''Prothrombin is activated by prothrombinase''' which consists of FXa, FVa, calcium, and a phospholipid surface. In vivo the first cleavage occurs at the R320-I321 bond, corresponding to residues 15-16 in ~~thrombin~~ which is the N-terminus of the B chain, producing meizothrombin.<ref name='seven'>PMID: 22944689</ref> Subsequent cleavage at R271-T272 yields thrombin.<ref name='seven'/> The initial cleavage can also occur at R271 resulting in prethrombin-2 which will then be cleaved at R320 to produce thrombin.<ref>PMID: 1995649</ref>

'''Prothrombin is activated by prothrombinase''' which consists of FXa, FVa, calcium, and a phospholipid surface. In vivo the first cleavage occurs at the R320-I321 bond, corresponding to residues 15-16 in chymotrypsin which is the N-terminus of the B chain, producing meizothrombin.<ref name='seven'>PMID: 22944689</ref> Subsequent cleavage at R271-T272 yields thrombin.<ref name='seven'/> The initial cleavage can also occur at R271 resulting in prethrombin-2 which will then be cleaved at R320 to produce thrombin.<ref>PMID: 1995649</ref>

After cleavage by prothrombinase the new B chain '''N-terminus (Ile16) folds into the core protease domain''' and forms a salt bridge with Asp194.<ref name='seven'/> This leads to stabilization of regions of the 180s-loop, Na+ binding loop, and γ-loop (zymogen activation domains). These changes provide the '''correct conformation for the S1 pocket and oxyanion hole for catalysis'''.<ref name='seven'/><ref>PMID: 15890651</ref>

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 Prothrombin is the zymogen form of thrombin. From N-terminal to C-terminal it consists of a Gla domain, two kringle domains, and a catalytic domain. The Gla domain is formed by vitamin K dependent carboxylation of glutamate residues.<ref>PMID: 18374193</ref>
-'''Prothrombin is activated by prothrombinase''' which consists of FXa, FVa, calcium, and a phospholipid surface. In vivo the first cleavage occurs at the R320-I321 bond, corresponding to residues 15-16 in thrombin which is the N-terminus of the B chain, producing meizothrombin.<ref name='seven'>PMID: 22944689</ref> Subsequent cleavage at R271-T272 yields thrombin.<ref name='seven'/> The initial cleavage can also occur at R271 resulting in prethrombin-2 which will then be cleaved at R320 to produce thrombin.<ref>PMID: 1995649</ref>
+'''Prothrombin is activated by prothrombinase''' which consists of FXa, FVa, calcium, and a phospholipid surface. In vivo the first cleavage occurs at the R320-I321 bond, corresponding to residues 15-16 in chymotrypsin which is the N-terminus of the B chain, producing meizothrombin.<ref name='seven'>PMID: 22944689</ref> Subsequent cleavage at R271-T272 yields thrombin.<ref name='seven'/> The initial cleavage can also occur at R271 resulting in prethrombin-2 which will then be cleaved at R320 to produce thrombin.<ref>PMID: 1995649</ref>
 After cleavage by prothrombinase the new B chain '''N-terminus (Ile16) folds into the core protease domain''' and forms a salt bridge with Asp194.<ref name='seven'/> This leads to stabilization of regions of the 180s-loop, Na+ binding loop, and γ-loop (zymogen activation domains). These changes provide the '''correct conformation for the S1 pocket and oxyanion hole for catalysis'''.<ref name='seven'/><ref>PMID: 15890651</ref>