1f0t

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spinqualitylabelsall models 1f0t, resolution 1.8Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

BOVINE TRYPSIN COMPLEXED WITH RPR131247

Overview

Involved in the coagulation cascade, factor Xa (FXa) is a serine protease, which has received great interest as a potential target for the, development of new antithrombotics. Although there is a great wealth of, structural data on thrombin complexes, few structures of ligand/FXa, complexes have been reported, presumably because of the difficulty in, growing crystals. Reproducible crystallization conditions for human, des-Gla1-45 coagulation FXa have been found. This has led to an, improvement in the diffraction quality of the crystals (about 2.1 A) when, compared to the previously reported forms (2.3-2.8 A) thus providing a, suitable platform for a structure-based drug design approach. A series of, crystal structures of noncovalent inhibitors complexed with FXa have been, determined, three of which are presented herein. These include compounds, containing the benzamidine moiety and surrogates of the basic group. The, benzamidine-containing compound binds in a canonical fashion typical of, synthetic serine protease inhibitors. On the contrary, molecules that, contain surrogates of the benzamidine group do not make direct, hydrogen-bonding interactions with the carboxylate of Asp189 at the bottom, of the S1 pocket. The structural data provide a likely explanation for the, specificity of these inhibitors and a great aid in the design of, bioavailable potent FXa inhibitors.

About this Structure

1F0T is a Single protein structure of sequence from Bos taurus with CA, SO4 and PR1 as ligands. Active as Trypsin, with EC number 3.4.21.4 Full crystallographic information is available from OCA.

Reference

Crystal structures of human factor Xa complexed with potent inhibitors., Maignan S, Guilloteau JP, Pouzieux S, Choi-Sledeski YM, Becker MR, Klein SI, Ewing WR, Pauls HW, Spada AP, Mikol V, J Med Chem. 2000 Aug 24;43(17):3226-32. PMID:10966741

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