Sandbox Reserved 348: Difference between revisions
From Proteopedia
Jump to navigationJump to search
Scene edits, added regulation section. |
Added images. |
||
| Line 12: | Line 12: | ||
==Structure== | ==Structure== | ||
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. | 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."/> | |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."/> | ||
|[[Image:Thrombin_catalytic_triad.png|thumb|left|150px|The [[serine protease]] catalytic triad in the active site of α-thrombin, bound to D-Phe-Pro-Arg chloromethylketone ligand.]] | |||
|} | |||
==Regulation== | ==Regulation== | ||
{| | |||
|[[Image:Thrombin-Hirudin_Complex.png|thumb|left|200px|<scene name='Sandbox_Reserved_348/Hirudin/2'>α-Thrombin - Hirudin Complex</scene>]] | |||
|Prothrombin is proteolytically activated to α-thrombin by [[factor Xa]]. α-Thrombin is permanently inactivated by the [[Serine Protease Inhibitor]] [[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."/> | |||
[[Hirudin]] is a potent natural inhibitor of thrombin, produced by [http://en.wikipedia.org/wiki/Leeches leeches] such as <I>[http://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis]</I>. | |||
|} | |||
==3D Structures== | ==3D Structures== | ||
===α-Thrombin=== | ===α-Thrombin=== | ||
| Line 33: | Line 38: | ||
*[[Serine Protease]] | *[[Serine Protease]] | ||
*[[Factor Xa]] | *[[Factor Xa]] | ||
*[[Hirudin]] | |||
==External Resources== | ==External Resources== | ||
