The critical role of hinge-region expulsion in the induced-fit heparin binding mechanism of antithrombin.

ABSTRACT: Antithrombin (AT) is the most important inhibitor of coagulation proteases. Its activity is stimulated by glycosaminoglycans, such as heparin, through allosteric and template mechanisms. AT utilises an induced-fit mechanism to bind with high affinity to a pentasaccharide sequence found in about one-third of heparin chains. The conformational changes behind this mechanism have been characterised by several crystal structures of AT in the absence and in the presence of pentasaccharide. Pentasaccharide binding ultimately results in a conformational change that improves affinity by about 1000-fold. Crystal structures show several differences, including the expulsion of the hinge region of the reactive centre loop from beta-sheet A, which is known to be critical for the allosteric activation of

SUBMITTER: Langdown J 

PROVIDER: S-EPMC2697666 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature