Author: Rezaie, Alireza R.

Source: Mini Reviews in Medicinal Chemistry, Volume 6, Number 8, August 2006 , pp. 859-865(7)

Publisher: Bentham Science Publishers

Abstract:

Factor Xa (fXa) is the vitamin K-dependent serine protease of the prothrombinase complex (fXa, factor Va, negatively charged membrane, and calcium) which is responsible for the conversion of prothrombin to thrombin in the final stage of the coagulation cascade. The proteolytic activity of fXa in plasma is primarily regulated by three physiological inhibitors, antithrombin (AT), protein Z-dependent protease inhibitor (ZPI) and tissue factor pathway inhibitor (TFPI). The first two inhibitors belong to the serpin family of plasma inhibitors, both of which require cofactors for their effective interaction with fXa. Thus, the AT interaction with the heparin-like glycosaminoglycans on the surface of the endothelium, and the ZPI complex formation with protein Z on membrane phospholipids is required for the physiological regulation of fXa by both serpins. On the other hand, TFPI is a slow and tight-binding, Kunitz type inhibitor that is capable of rapidly inhibiting fXa independent of a cofactor. This article will review the structural features that enable fXa to specifically interact with these three inhibitors under different conditions.

Keywords: Factor Xa; antithrombin; PZ-dependent protease inhibitor; Tissue factor pathway inhibitor; Serpin; Kunitz inhibitor

Document Type: Research article

DOI: http://dx.doi.org/10.2174/138955706777935017

Affiliations: 1: Department of Biochemistry and Molecular Biology, St. Louis University School of Medicine, 1402 S.Grand Blvd., St. Louis, MO 63104, USA.

Publication date: 2006-08-01

More about this publication?

• The aim of Mini-Reviews in Medicinal Chemistry is to publish short reviews on the important recent developments in medicinal chemistry and allied disciplines.
  
  The scope of Mini-Reviews in Medicinal Chemistry will cover all areas of medicinal chemistry including developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, combinatorial chemistry, drug targets, and natural product research and structure-activity relationship studies.
  
  Mini-Reviews in Medicinal Chemistry is an essential journal for every medicinal and pharmaceutical chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

Related content

• In this: publication
• By this: publisher
• In this Subject: Chemistry (General) ,  Pharmacology
• By this author: Rezaie, Alireza R.

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers