1hxe

From Proteopedia

Revision as of 14:23, 18 December 2007

SERINE PROTEASE

Overview

When Na+ binds to thrombin, a conformational change is induced that, renders the enzyme kinetically faster and more specific in the activation, of fibrinogen. Two Na+ binding sites have here been identified, crystallographically by exchanging Na+ with Rb+. One is intermolecular, found on the surface between two symmetry-related thrombin molecules., Since it is not present in thrombin crystal structures having different, crystal systems, the other Na+ site is the functionally relevant one. The, second site has octahedral coordination with the carbonyl oxygen atoms of, Arg221A and Lys224 and four conserved water molecules. It is located near, Asp189 of the S1 specificity site in an elongated solvent channel (8 x 18, A) formed by four antiparallel beta-strands between Cys182-Cys191 and, Val213-Tyr228. This channel, extending from the active site to the, opposite surface of the enzyme, was first noted in the hirudin-thrombin, structure and contains about 20 conserved water molecules linked together, by a hydrogen bonding network that connects to the main chain of thrombin., Although the antiparallel beta-strand interactions of the functional Na+, binding site are the same in prethrombin2, the loops between the strands, are very different, so that Asp189 and Arg221A are not positioned properly, for either substrate or Na+ binding in prethrombin2. A water molecule with, octahedral coordination has also been identified in factor Xa at the, topologically equivalent Na+ site position of thrombin. Since activated, protein C shows enhanced activity with monovalant cation binding, the same, position is probably utilized by Na+. Since thrombin crystals could not be, grown in the absence of Na+, the cation was leached from Na(+)-bound, thrombin crystals by diffusion/exchange. Although both Na+ and their, coordinating water molecules were removed from the Na+ binding sites, the, remainder of the thrombin structure was, unexpectedly, the same. The lack, of an allosteric change is most likely attributable to crystal packing, effects. Thus, the structure of the slow form remains to be established, crystallographically.

Disease

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

About this Structure

1HXE is a Protein complex structure of sequences from Homo sapiens with RB as ligand. Active as Thrombin, with EC number 3.4.21.5 Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

The molecular environment of the Na+ binding site of thrombin., Zhang E, Tulinsky A, Biophys Chem. 1997 Jan 31;63(2-3):185-200. PMID:9108691

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