Factor XIa: Difference between revisions
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===Introduction=== | ===Introduction=== | ||
Factor XIa is unique protease derived from the activation of the coagulation zymogen, factor XI. Factor XIa partcipates in the procoagulant response via contact activation pathway. Synthesized by the liver similar to most vitamin K-dependent coagulation proteins, the zymogen, factor XI circulates in plasma as a 160 kDa disulfide-linked homodimer in complex with high molecular weight kininogen (HK)<ref>PMID:915004</ref>. Studies show that factor XI is a substrate for various plasma proteins such as factor XIIa, thrombin, meizothrombin and factor XIa (via autoactivation). Proteolysis of the <scene name='Sandbox/Arg369-ile370/1'> Arg369-Ile370</scene> bond generates the active enzyme factor XIa which in turn cleaves its substrate factor factor IX to produce the serine protease factor IXa. | Factor XIa is unique protease derived from the activation of the coagulation zymogen, factor XI. Factor XIa partcipates in the procoagulant response via contact activation pathway. Synthesized by the liver similar to most vitamin K-dependent coagulation proteins, the zymogen, factor XI circulates in plasma as a 160 kDa disulfide-linked homodimer in complex with high molecular weight kininogen (HK)<ref>PMID:915004</ref>. Studies show that factor XI is a substrate for various plasma proteins such as factor XIIa, thrombin, meizothrombin and factor XIa (via autoactivation). Proteolysis of the <scene name='Sandbox/Arg369-ile370/1'> Arg369-Ile370</scene> bond generates the active enzyme factor XIa which in turn cleaves its substrate factor factor IX to produce the serine protease factor IXa. | ||
<Structure load='2f83' size='350' frame='true' align='right' caption=' Crystal structure of factor XI' /> | <Structure load='2f83' size='350' frame='true' align='right' caption=' Crystal structure of factor XI [[2f83]]' /> | ||
==Protein Structure== | ==Protein Structure== | ||
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==Formation of Factor XIa== | ==Formation of Factor XIa== | ||
<Structure load='3bg8' size='350' frame='true' align='right' caption='Factor XIa light chain'/> | <Structure load='3bg8' size='350' frame='true' align='right' caption='Factor XIa light chain[[3bg8]]'/> | ||
Factor XI is partially proteolyzed ''in vitro'' by thrombin and factor XIIa generating the active serine-protease, factor XIa. Similar to other chymotrypsin-like proteases, its topology consist of two β-barrels linked through a central loop. Next to the C-terminal Cys-356 of the factor XI heavy chain, the polypeptide forms a 3-10 helix conformation and again turn sharply 90 degrees at Cys-362 forming a disulfide bond with Cys-482 within the active site region. | Factor XI is partially proteolyzed ''in vitro'' by thrombin and factor XIIa generating the active serine-protease, factor XIa. Similar to other chymotrypsin-like proteases, its topology consist of two β-barrels linked through a central loop. Next to the C-terminal Cys-356 of the factor XI heavy chain, the polypeptide forms a 3-10 helix conformation and again turn sharply 90 degrees at Cys-362 forming a disulfide bond with Cys-482 within the active site region. | ||