From Proteopedia
proteopedia linkproteopedia link
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
|
|
1ppb, resolution 1.92Å ()
|
Ligands:
|
|
Activity:
| Thrombin, with EC number 3.4.21.5
|
Structural annotation:
|
Resources:
| CATH : 1Ppbh01, 1Ppbh02 InterPro : Ipr000001, Ipr009003, Ipr017857, Ipr003966, Ipr018992, Ipr013806, Ipr018056, Ipr001254, Ipr018114, Ipr000294, Ipr001314 Pfam : PF00089, PF09396 SCOP : d1ppb.1
|
|
|
Resources:
| FirstGlance, OCA, RCSB, PDBsum
|
Coordinates:
| save as pdb, mmCIF, xml
|
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]
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.
|
Regulation
| 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
- ↑ 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
- ↑ Degen SJ, Davie EW. Nucleotide sequence of the gene for human prothrombin. Biochemistry. 1987 Sep 22;26(19):6165-77. PMID:2825773
- ↑ 3.0 3.1 3.2 Di Cera E. Thrombin interactions. Chest. 2003 Sep;124(3 Suppl):11S-7S. PMID:12970119
- ↑ 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