1HRT

THE STRUCTURE OF A COMPLEX OF BOVINE ALPHA-THROMBIN AND RECOMBINANT HIRUDIN AT 2.8 ANGSTROMS RESOLUTION

Summary for 1HRT

• Entry DOI: 10.2210/pdb1hrt/pdb
• Descriptor: THROMBIN (SMALL SUBUNIT), THROMBIN (LARGE SUBUNIT), HIRUDIN, ... (4 entities in total)
• Functional Keywords: serine proteinase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Bos taurus (cattle); More
• Cellular location: Secreted, extracellular space: P00735 P00735; Secreted: P01050
• Total number of polymer chains: 3
• Total formula weight: 42481.17

Authors

Vitali, J.,Edwards, B.F.P. (deposition date: 1993-02-25, release date: 1994-01-31, Last modification date: 2024-10-16)

Primary citation

Vitali, J.,Martin, P.D.,Malkowski, M.G.,Robertson, W.D.,Lazar, J.B.,Winant, R.C.,Johnson, P.H.,Edwards, B.F.
The structure of a complex of bovine alpha-thrombin and recombinant hirudin at 2.8-A resolution.
J.Biol.Chem., 267:17670-17678, 1992

PubMed Abstract: Crystals of the complex of bovine alpha-thrombin with recombinant hirudin variant 1 have space group C222(1) with cell constants a = 59.11, b = 102.62, and c = 143.26 A. The orientation and position of the thrombin component was determined by molecular replacement and the hirudin molecule was fit in 2 magnitude of Fo - magnitude of Fc electron density maps. The structure was refined by restrained least squares and simulated annealing to R = 0.161 at 2.8-A resolution. The binding of hirudin to thrombin is generally similar to that observed in the crystals of human thrombin-hirudin. Several differences in the interactions of the COOH-terminal polypeptide of hirudin, specifically of residues Asp-55h, Phe-56h, Glu-57h, and Glu-58h, and a few differences in the interactions of the hirudin core, specifically of residues Asp-5h, Ser-19h, and Asn-20h, with thrombin from human thrombin-hirudin suggest that there is some flexibility in the binding of these 2 molecules. Most of the residues in the 9 subsites that bind fibrinopeptide A7-16 to thrombin also interact with the NH2-terminal domain of hirudin. The S1 subsite is a notable exception in that only 1 of its 6 residues, namely Ser-214, interacts with hirudin. The only difference between human and bovine thrombins that appears to influence the binding of hirudin is the replacement of Lys-149E by an acidic glutamate in the bovine enzyme.

PubMed: 1517214

Experimental method

X-RAY DIFFRACTION (2.8 Å)