Sandbox Reserved 348: Difference between revisions
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{{ STRUCTURE_1ppb | PDB=1ppb | SCENE=Sandbox_Reserved_348/Ligand/ | {{ STRUCTURE_1ppb | PDB=1ppb | SCENE=Sandbox_Reserved_348/Ligand/4 }} | ||
[[Image:Thrombin_in_Coagulation.png|thumb|left|300px|The role of thrombin and prothrombin in [http://en.wikipedia.org/wiki/Coagulation coagulation].]] | [[Image:Thrombin_in_Coagulation.png|thumb|left|300px|The role of thrombin and prothrombin in [http://en.wikipedia.org/wiki/Coagulation coagulation].]] | ||
Thrombin is a [[trypsin]]-like [[ | Thrombin is a [[trypsin]]-like [[serine protease]] which is best known for its role in blood clotting. In humans, the F2 gene codes for prothrombin, which is also known as Coagulation Factor II.<ref name="Human genes encoding prothrombin and ceruloplasmin map to 11p11-q12 and 3q21-24, respectively.">PMID:3474786</ref><ref name="Nucleotide sequence of the gene for human prothrombin.">PMID:2825773</ref> Clevage of prothrombin to form activated α-thrombin is a key step in the final common pathway of blood clotting, because clevage by thrombin activates several factors in blood clotting, especially [[fibrin]], [[factor XIII]], and [[protein C]].<ref name="Thrombin interactions.">PMID:12970119</ref> | ||
__TOC__ | __TOC__ | ||
==Structure== | ==Structure== | ||
Thrombin is comprised of two chains, often referred to as the <scene name='Sandbox_Reserved_348/Small_subunit/ | Thrombin is comprised of two chains, often referred to as the <scene name='Sandbox_Reserved_348/Small_subunit/3'>short chain</scene> and the <scene name='Sandbox_Reserved_348/Large_subunit/3'>long chain</scene>. All known functional epitopes are found on the long chain. There is one active site, which in the case of [[1ppb]] is occupied with <scene name='Sandbox_Reserved_348/Ligand/4'>D-Phe-Pro-Arg chloromethylketone</scene>.<ref name="The refined 1.9A crystal structure of human alpha-thrombin: interaction with D-Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment.">PMID:2583108</ref> Additionally, there are three structural disulfide bonds. | ||
While thrombin is described as a [[trypsin]]-like [[serine protease]], it is more specific than trypsin due to two exosites which bind the substrate at a point separate from the active site. These exosites also allow for more specific inhibition, since [[protein C]] and [[factor Xa]] have similar active sites but play very different roles in the clotting process.<ref name="Thrombin interactions."/> | |||
==Regulation== | |||
Prothrombin is proteolytically activated to α-thrombin by [[factor Xa]]. α-Thrombin is permanently inactivated by [[antithrombin]], with [[heparin]] as a cofactor, and allosterically regulated by sodium ion concentration. [[Thrombomodulin]] inhibits clevage of fibrinogen to fibrin, but also enhances α-thrombin activity with respect to [[protein C]]. Since activated protein C proteolytically inactivates earlier steps in the chain, this effectively reverses the role of thrombin from coagulant to anticoagulant.<ref name="Thrombin interactions."/> | |||
==3D Structures== | ==3D Structures== | ||
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*[[Trypsin]] | *[[Trypsin]] | ||
*[[Serine Protease]] | *[[Serine Protease]] | ||
*[[Factor Xa]] | |||
==External Resources== | ==External Resources== | ||
