1nu7
Staphylocoagulase-Thrombin Complex
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OverviewOverview
Many bacterial pathogens secrete proteins that activate host, trypsinogen-like enzyme precursors, most notably the proenzymes of the, blood coagulation and fibrinolysis systems. Staphylococcus aureus, an, important human pathogen implicated in sepsis and endocarditis, secretes, the cofactor staphylocoagulase, which activates prothrombin, without the, usual proteolytic cleavages, to directly initiate blood clotting. Here we, present the 2.2 A crystal structures of human alpha-thrombin and, prethrombin-2 bound to a fully active staphylocoagulase variant. The, cofactor consists of two domains, each with three-helix bundles; this is a, novel fold that is distinct from known serine proteinase activators, particularly the streptococcal plasminogen activator streptokinase. The, staphylocoagulase fold is conserved in other bacterial, plasma-protein-binding factors and extracellular-matrix-binding factors., Kinetic studies confirm the importance of isoleucine 1 and valine 2 at the, amino terminus of staphylocoagulase for zymogen activation. In addition to, making contacts with the 148 loop and (pro)exosite I of prethrombin-2, staphylocoagulase inserts its N-terminal peptide into the activation, pocket of bound prethrombin-2, allosterically inducing functional, catalytic machinery. These investigations demonstrate unambiguously the, validity of the zymogen-activation mechanism known as 'molecular, sexuality'.
DiseaseDisease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this StructureAbout this Structure
1NU7 is a Protein complex structure of sequences from Homo sapiens and Staphylococcus aureus with HG, MCR and IMD as ligands. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.
ReferenceReference
Staphylocoagulase is a prototype for the mechanism of cofactor-induced zymogen activation., Friedrich R, Panizzi P, Fuentes-Prior P, Richter K, Verhamme I, Anderson PJ, Kawabata S, Huber R, Bode W, Bock PE, Nature. 2003 Oct 2;425(6957):535-9. PMID:14523451
Page seeded by OCA on Mon Nov 12 18:25:21 2007