1DOJ

Crystal structure of human alpha-thrombin*RWJ-51438 complex at 1.7 A

Summary for 1DOJ

• Entry DOI: 10.2210/pdb1doj/pdb
• Related: 1abj
• Related PRD ID: PRD_000623
• Descriptor: ALPHA-THROMBIN, HIRUGEN, N-methyl-D-phenylalanyl-N-{(1S)-4-carbamimidamido-1-[(6-carboxy-1,3-benzothiazol-2-yl)carbonyl]butyl}-L-prolinamide, ... (6 entities in total)
• Functional Keywords: thrombin, serine protease, enzyme inhibition, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 36211.14

Authors

Recacha, R.,Costanzo, M.J.,Maryanoff, B.E.,Carson, M.,DeLucas, L.,Chattopadhyay, D. (deposition date: 1999-12-21, release date: 2000-11-03, Last modification date: 2024-10-30)

Primary citation

Recacha, R.,Costanzo, M.J.,Maryanoff, B.E.,Carson, M.,DeLucas, L.,Chattopadhyay, D.
Structure of human alpha-thrombin complexed with RWJ-51438 at 1.7 A: unusual perturbation of the 60A-60I insertion loop.
Acta Crystallogr.,Sect.D, 56:1395-1400, 2000

PubMed Abstract: The three-dimensional structure of the ternary complex consisting of human alpha-thrombin, hirugen and the active-site inhibitor RWJ-51438 has been determined at 1.7 A resolution. The crystals of the complex belong to the orthorhombic space group P2(1)2(1)2, with unit-cell parameters a = 62.98, b = 117.52, c = 47.99 A. The refined R and R(free) values are 0.196 and 0.232, respectively. The ketone carbonyl group of the inhibitor is covalently linked to the hydroxyl O atom of Ser195, forming a tetrahedral intermediate hemiketal structure; the benzothiazole ring N atom of RWJ-51438 forms a hydrogen bond with His57. Surprisingly, the carboxylate substituent on the benzothiazole group forms salt bridges with Lys60F NZ and the NZ of the symmetry-related residues Lys236 and Lys240, which introduces steric effects that perturb the 60A-60I insertion loop, especially at residues Trp60D and Phe60H.

PubMed: 11053836
DOI: 10.1107/S0907444900010763

Experimental method

X-RAY DIFFRACTION (1.7 Å)