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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

12 Issues per year


IMPACT FACTOR 2016: 3.273

CiteScore 2016: 3.01

SCImago Journal Rank (SJR) 2016: 1.679
Source Normalized Impact per Paper (SNIP) 2016: 0.800

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1437-4315
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Volume 393, Issue 9 (Sep 2012)

Issues

An ensemble view of thrombin allostery

Bernhard C. Lechtenberg
  • Cambridge Institute for Medical Research, Department of Haematology, University of Cambridge, Cambridge, CB2 0XY, UK
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Stefan M.V. Freund / James A. Huntington
  • Corresponding author
  • Cambridge Institute for Medical Research, Department of Haematology, University of Cambridge, Cambridge, CB2 0XY, UK
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar

Abstract

Thrombin is the central protease of the coagulation cascade. Its activity is tightly regulated to ensure rapid blood clotting while preventing uncontrolled thrombosis. Thrombin interacts with multiple substrates and cofactors and is critically involved in both pro- and anticoagulant pathways of the coagulation network. Its allosteric regulation, especially by the monovalent cation Na+, has been the focus of research for more than 30 years. It is believed that thrombin can adopt an anticoagulant (‘slow’) conformation and, after Na+ binding, a structurally distinct procoagulant (‘fast’) state. In the past few years, however, the general view of allostery has evolved from one of rigid structural changes towards thermodynamic ensembles of conformational states. With this background, the view of the allosteric regulation of thrombin has also changed. The static view of the two-state model has been dismissed in favor of a more dynamic view of thrombin allostery. Herein, we review recent data that demonstrate that apo-thrombin is zymogen-like and exists as an ensemble of conformations. Furthermore, we describe how ligand binding to thrombin allosterically stabilizes conformations on the continuum from zymogen to protease.

Keywords: coagulation; NMR spectroscopy; plasticity; protease; zymogen

About the article

Corresponding author


Received: 2012-04-16

Accepted: 2012-05-24

Published in Print: 2012-09-01


Citation Information: , ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2012-0178.

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©2012 by Walter de Gruyter Berlin Boston. Copyright Clearance Center

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