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The structure of a complex of recombinant hirudin and human alpha-thrombin.
Department of Chemistry, Michigan State University, East Lansing 48824.
The crystallographic structure of a recombinant hirudin-thrombin complex has been solved at 2.3 angstrom (A) resolution. Hirudin consists of an NH2-terminal globular domain and a long (39 A) COOH-terminal extended domain. Residues Ile1 to Tyr3 of hirudin form a parallel beta-strand with Ser214 to Glu217 of thrombin with the nitrogen atom of Ile1 making a hydrogen bond with Ser195 O gamma atom of the catalytic site, but the specificity pocket of thrombin is not involved in the interaction. The COOH-terminal segment makes numerous electrostatic interactions with an anion-binding exosite of thrombin, whereas the last five residues are in a helical loop that forms many hydrophobic contacts. In all, 27 of the 65 residues of hirudin have contacts less than 4.0 A with thrombin (10 ion pairs and 23 hydrogen bonds). Such abundant interactions may account for the high affinity and specificity of hirudin.
PMID: 2374926 [PubMed - indexed for MEDLINE]
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Cited by 61 PubMed Central articles
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Macedo-Ribeiro S, Almeida C, Calisto BM, Friedrich T, Mentele R, Stürzebecher J, Fuentes-Prior P, Pereira PJ.
PLoS One. 2008 Feb 20; 3(2):e1624. Epub 2008 Feb 20.
[PLoS One. 2008]
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Crystal structure of a biosynthetic sulfo-hirudin complexed to thrombin.
Liu CC, Brustad E, Liu W, Schultz PG.
J Am Chem Soc. 2007 Sep 5; 129(35):10648-9. Epub 2007 Aug 9.
[J Am Chem Soc. 2007]
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ReviewHuman inhibitor of apoptosis proteins: why XIAP is the black sheep of the family.
Eckelman BP, Salvesen GS, Scott FL.
EMBO Rep. 2006 Oct; 7(10):988-94.
[EMBO Rep. 2006]
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Structures reported by this article