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Staphylocoagulase

  • Peter PanizziEmail author
  • Heather K. Kroh
  • Pablo Fuentes-Prior
  • Paul E. Bock
Chapter

Abstract

Staphylocoagulase (SC) is a protein secreted by most strains of Staphylococcus aureus, a potent human pathogenic bacterium. SC causes blood clotting by direct activation of the thrombin precursor, prothrombin (ProT). This occurs through a non-proteolytic, cofactor-induced mechanism of activation called “molecular sexuality”. The 2.2 Å crystal structure of a fully active SC fragment in complex with the ProT catalytic domain, prethrombin 2, proved the molecular sexuality mechanism. Recent structural and mechanistic studies have investigated how SC specifically activates ProT to cause fibrin generation through association of active SC·ProT* complexes with fibrinogen. In addition, a predicted structural homolog of SC has been identified from S. aureus, called von Willebrand factor-binding protein (VWbp). VWbp also activates human ProT by the molecular sexuality mechanism, but it displays additional regulation of its specificity through a novel hysteretic kinetic mechanism. The mechanisms used by both of these bacterial ProT activators to subvert the human coagulation system offers new insight into the role of secreted exoproteins in staphylococcal infection, as well as alternative pathways for targeted treatment of staphylococcal coagulopathies.

Keywords

Fibrinogen Binding Free Thrombin Bovine Trypsinogen Thrombin Precursor Human ProT 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

Research from the authors’ laboratories was supported by National Institutes of Health Grant R37 HL071544 from the Heart, Lung, and Blood Institute to P. E. B., F32 HL094010 and K99 HL094533 to P. P., and SAF2007-64140 from Spanish Ministerio de Ciencia e Innovación (MICINN) to P. F.-P. H.K.K. was supported in part by NIH Training Grant T32 HL07751.

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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Peter Panizzi
    • 1
    Email author
  • Heather K. Kroh
    • 2
  • Pablo Fuentes-Prior
    • 3
  • Paul E. Bock
    • 2
  1. 1.Center for Systems BiologyMassachusetts General HospitalBostonUSA
  2. 2.Department of PathologyVanderbilt University School of MedicineNashvilleUSA
  3. 3.Institut de Recerca, Hospital de la Santa Creu i Sant PauBarcelonaSpain

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