2a1d
From Proteopedia
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'''Staphylocoagulase bound to bovine thrombin''' | '''Staphylocoagulase bound to bovine thrombin''' | ||
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[[Category: Kawabata, S.]] | [[Category: Kawabata, S.]] | ||
[[Category: Panizzi, P.]] | [[Category: Panizzi, P.]] | ||
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| - | [[Category: | + | [[Category: Prothrombin activator]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 18:28:57 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 15:28, 3 May 2008
Staphylocoagulase bound to bovine thrombin
Overview
Staphylocoagulase (SC) is a protein secreted by the human pathogen, Staphylococcus aureus, that activates human prothrombin (ProT) by inducing a conformational change. SC-bound ProT efficiently clots fibrinogen, thus bypassing the physiological blood coagulation pathway. The crystal structure of a fully active SC fragment, SC-(1-325), bound to human prethrombin 2 showed that the SC-(1-325) N terminus inserts into the Ile(16) pocket of prethrombin 2, thereby inducing expression of a functional catalytic site in the cognate zymogen without peptide bond cleavage. As shown here, SC-(1-325) binds to bovine and human ProT with similar affinity but activates the bovine zymogen only very poorly. By contrast to the approximately 2-fold difference in chromogenic substrate kinetic constants between human thrombin and the SC-(1-325).human (pro)thrombin complexes, SC-(1-325).bovine ProT shows a 3,500-fold lower k(cat)/K(m) compared with free bovine thrombin, because of a 47-fold increase in K(m) and a 67-fold decrease in k(cat). The SC-(1-325).bovine ProT complex is approximately 5,800-fold less active compared with its human counterpart. Comparison of human and bovine fibrinogen as substrates of human and bovine thrombin and the SC-(1-325).(pro)thrombin complexes indicates that the species specificity of SC-(1-325) cofactor activity is determined primarily by differences in conformational activation of bound ProT. These results suggest that the catalytic site in the SC-(1-325).bovine ProT complex is incompletely formed. The current crystal structure of SC-(1-325).bovine thrombin reveals that SC would dock similarly to the bovine proenzyme, whereas the bovine (pro)thrombin-characteristic residues Arg(144) and Arg(145) would likely interfere with insertion of the SC N terminus, thus explaining the greatly reduced activation of bovine ProT.
About this Structure
2A1D is a Protein complex structure of sequences from Bos taurus and Staphylococcus aureus. Full crystallographic information is available from OCA.
Reference
Structural basis for reduced staphylocoagulase-mediated bovine prothrombin activation., Friedrich R, Panizzi P, Kawabata S, Bode W, Bock PE, Fuentes-Prior P, J Biol Chem. 2006 Jan 13;281(2):1188-95. Epub 2005 Oct 17. PMID:16230338 Page seeded by OCA on Sat May 3 18:28:57 2008
