Exosites expedite blood coagulation

Author(s)

Oliva, Maria Luiza Vilela ; Dreveny, Ingrid ; Emsley, Jonas

• Document type: Journal article
• Source: Journal of Biological Chemistry; v. 295, n. 45, p. 2-pg., 2020-11-06.

Abstract

A careful balance between active-site and exosite contributions is critically important for the specificity of many proteases, but this balance is not yet defined for some of the serine proteases that serve as coagulation factors. Basavaraj and Krishnaswamy have closed an important gap in our knowledge of coagulation factor X activation by the intrinsic Xase complex by showing that exosite binding plays a critical role in this process, which they describe as a "dock and lock." This finding not only significantly enhances our understanding of this step in the coagulation cascade and highlights parallels with the prothrombinase complex, but will also provide a novel rationale for inhibitor development in the future. (AU)

• FAPESP's process: 19/22243-9 - Fragments derived from the structure of protease inhibitors with selectivity for inhibition of mammalian and microorganism enzymes and its role as an anti-inflammatory, antimicrobial, antithrombotic and anti- tumor agent: mechanism of action
• Grantee: Camila Ramalho Bonturi
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/06630-7 - Fragments derived from the structure of protease inhibitors with selectivity for inhibition of mammalian and microorganism enzymes and its role as an anti-inflammatory, antimicrobial, antithrombotic and anti- tumor agent: mechanism of action
• Grantee: Maria Luiza Vilela Oliva
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/07972-9 - Development of lead agents for prophylaxis and treatment of cardiovascular diseases
• Grantee: Maria Luiza Vilela Oliva
• Support Opportunities: Regular Research Grants