Thrombin: Difference between revisions
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By balancing substrate specificity, activity, and inhibition thrombin plays a central role in the blood coagulation cascade. <ref name="three"/> | By balancing substrate specificity, activity, and inhibition thrombin plays a central role in the blood coagulation cascade. <ref name="three"/> | ||
[[Image:Substrates.png| | [[Image:Substrates.png|450px|center|thumb| Coagulation related substrates of thrombin, excluding serpin inhibitors.]] | ||
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==The Thrombin Life Cycle== | ==The Thrombin Life Cycle== | ||
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==Prothrombin Activation== | ==Prothrombin Activation== | ||
[[Image:Prothrombin activation scheme_3.png| | [[Image:Prothrombin activation scheme_3.png|450px|left|thumb| Activation scheme of in vivo activation of prothrombin by FXa in the absence of FVa.]] | ||
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[[Image:Prothrombin activation scheme_nofva3.png| | [[Image:Prothrombin activation scheme_nofva3.png|450px|left|thumb| Activation scheme of in vivo activation of prothrombin by the prothrombinase complex in presence of calcium and a phospholipid bilayer]] | ||
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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 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> | ||
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==Structure and Function== | ==Structure and Function== | ||
[[Image:Electrostatic labeled.png| | [[Image:Electrostatic labeled.png|450px|right|thumb| Thrombin (1PPB) overlayed with electrostatic surface. Structural features 60-loop, γ-loop, exosite I, and exosite II labeled]] | ||
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Thrombin is a α/β heterodimer composed of a 36 amino acid A chain and 259 amino acid B chain connected by a <scene name='58/583418/Disulfides_nospin/1'>disufide</scene> bridge between Cys1 and Cys122, in addition to 3 other intrachain disulfide bonds.<ref name='eight'>PMID: 2583108</ref> Its overall fold is similar to trypsin and chymotrypsin and it belongs to the [http://merops.sanger.ac.uk/cgi-bin/famsum?family=s1 peptidase S1 protease family]<ref>PMID: 18768474</ref>. It is an overall spherical protein with approximate dimensions of 45 Å X 45 Å X 50 Å.<ref name='eight'/> | Thrombin is a α/β heterodimer composed of a 36 amino acid A chain and 259 amino acid B chain connected by a <scene name='58/583418/Disulfides_nospin/1'>disufide</scene> bridge between Cys1 and Cys122, in addition to 3 other intrachain disulfide bonds.<ref name='eight'>PMID: 2583108</ref> Its overall fold is similar to trypsin and chymotrypsin and it belongs to the [http://merops.sanger.ac.uk/cgi-bin/famsum?family=s1 peptidase S1 protease family]<ref>PMID: 18768474</ref>. It is an overall spherical protein with approximate dimensions of 45 Å X 45 Å X 50 Å.<ref name='eight'/> | ||