3HTC

THE STRUCTURE OF A COMPLEX OF RECOMBINANT HIRUDIN AND HUMAN ALPHA-THROMBIN

Summary for 3HTC

• Entry DOI: 10.2210/pdb3htc/pdb
• Descriptor: ALPHA-THROMBIN (SMALL SUBUNIT), ALPHA-THROMBIN (LARGE SUBUNIT), HIRUDIN VARIANT 2 (3 entities in total)
• Functional Keywords: hydrolase(serine protease)
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted, extracellular space: P00734 P00734; Secreted: P09945
• Total number of polymer chains: 3
• Total formula weight: 40794.26

Authors

Tulinsky, A.,Rydel, T.J.,Ravichandran, K.G.,Huber, R.,Bode, W. (deposition date: 1993-06-11, release date: 1994-01-31, Last modification date: 2024-02-21)

Primary citation

Rydel, T.J.,Ravichandran, K.G.,Tulinsky, A.,Bode, W.,Huber, R.,Roitsch, C.,Fenton 2nd., J.W.
The structure of a complex of recombinant hirudin and human alpha-thrombin.
Science, 249:277-280, 1990

PubMed Abstract: 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.

PubMed: 2374926

Experimental method

X-RAY DIFFRACTION (2.3 Å)