2a1d
From Proteopedia
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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 with NDG and NA as ligands. Active as Thrombin, with EC number 3.4.21.5 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 Wed Nov 21 07:51:55 2007
