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Sandbox Reserved 348

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This Sandbox is Reserved from January 10, 2010, through April 10, 2011 for use in BCMB 307-Proteins course taught by Andrea Gorrell at the University of Northern British Columbia, Prince George, BC, Canada.
To get started:
  • Click the edit this page tab at the top. Save the page after each step, then edit it again.
  • Click the 3D button (when editing, above the wikitext box) to insert Jmol.
  • show the Scene authoring tools, create a molecular scene, and save it. Copy the green link into the page.
  • Add a description of your scene. Use the buttons above the wikitext box for bold, italics, links, headlines, etc.

More help: Help:Editing


PDB ID 1ppb

Drag the structure with the mouse to rotate
1ppb, resolution 1.92Å ()
Ligands:
Activity: Thrombin, with EC number 3.4.21.5
Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml


The role of thrombin and prothrombin in coagulation.
The role of thrombin and prothrombin in coagulation.

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.[1][2] 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.[3]

Contents


Structure

Thrombin is comprised of two chains, often referred to as the and the . All known functional epitopes are found on the long chain. There is one active site, which in the case of 1ppb is occupied with .[4] 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.[3]
The serine protease catalytic triad in the active site of α-thrombin, bound to D-Phe-Pro-Arg chloromethylketone ligand.
The serine protease catalytic triad in the active site of α-thrombin, bound to D-Phe-Pro-Arg chloromethylketone ligand.

Regulation

jmolSetTarget('1');jmolLink('State; message Scene_finished;\'); scn = scn.replace(\'_setState;\', \'_setState; setButtonsStartingState();\'); scn = scn.replace(\'DORESIZE\', \'\'); script inline scn;','α-Thrombin - Hirudin Complex','α-Thrombin - Hirudin Complex');
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.[3]

Hirudin is a potent natural inhibitor of thrombin, produced by leeches such as Hirudo medicinalis.

3D Structures

α-Thrombin

Prothrombin

See Also

External Resources

References

  1. ↑ Royle NJ, Irwin DM, Koschinsky ML, MacGillivray RT, Hamerton JL. Human genes encoding prothrombin and ceruloplasmin map to 11p11-q12 and 3q21-24, respectively. Somat Cell Mol Genet. 1987 May;13(3):285-92. PMID:3474786
  2. ↑ Degen SJ, Davie EW. Nucleotide sequence of the gene for human prothrombin. Biochemistry. 1987 Sep 22;26(19):6165-77. PMID:2825773
  3. ↑ 3.0 3.1 3.2 Di Cera E. Thrombin interactions. Chest. 2003 Sep;124(3 Suppl):11S-7S. PMID:12970119
  4. ↑ Bode W, Mayr I, Baumann U, Huber R, Stone SR, Hofsteenge J. The refined 1.9 A crystal structure of human alpha-thrombin: interaction with D-Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment. EMBO J. 1989 Nov;8(11):3467-75. PMID:2583108
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