1mh0

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1mh0, resolution 2.80Å

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Crystal structure of the anticoagulant slow form of thrombin

Contents

Overview

Using the thrombin mutant R77aA devoid of the site of autoproteolytic, degradation at exosite I, we have solved for the first time the structure, of thrombin free of any inhibitors and effector molecules and stabilized, in the Na(+)-free slow form. The slow form shows subtle differences, compared with the currently available structures of the Na(+)-bound fast, form that carry inhibitors at the active site or exosite I. The most, notable differences are the displacement of Asp-189 in the S1 specificity, pocket, a downward shift of the 190-193 strand, a rearrangement of the, side chain of Glu-192, and a significant shift in the position of the, catalytic Ser-195 that is no longer within H-bonding distance from His-57., The structure of the slow form explains the reduced specificity toward, synthetic and natural substrates and suggests a molecular basis for its, anticoagulant properties.

Disease

Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]

About this Structure

1MH0 is a Single protein structure of sequence from Homo sapiens with NAG as ligand. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.

Reference

Crystal structure of the anticoagulant slow form of thrombin., Pineda AO, Savvides SN, Waksman G, Di Cera E, J Biol Chem. 2002 Oct 25;277(43):40177-80. Epub 2002 Aug 29. PMID:12205081

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