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A novel antithrombin domain dictates the journey's end of a proteinase.

ABSTRACT: Antithrombin (AT) is an anticoagulant serpin that irreversibly inactivates the clotting proteinases factor Xa and thrombin by forming covalent complexes with them. Mutations in its critical domains, such as those that impair the conformational rearrangement required for proteinase inactivation, increase the risk of venous thrombosis. Águila et al. characterize for the first time the destabilizing effects of mutations in the region of AT that makes contact with the proteinase in the final acyl-enzyme complex. Their work adds new insight into the unique structural intricacies of the inhibitory mechanism.

SUBMITTER: Verhamme IM

PROVIDER: S-EPMC5633113 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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A novel antithrombin domain dictates the journey's end of a proteinase.

Verhamme Ingrid M IM

The Journal of biological chemistry 20171001 40

Antithrombin (AT) is an anticoagulant serpin that irreversibly inactivates the clotting proteinases factor Xa and thrombin by forming covalent complexes with them. Mutations in its critical domains, such as those that impair the conformational rearrangement required for proteinase inactivation, increase the risk of venous thrombosis. Águila <i>et al.</i> characterize for the first time the destabilizing effects of mutations in the region of AT that makes contact with the proteinase in the final ...[more]

PMID: 28986431

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