1d4p

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spinqualitylabelsall models 1d4p, resolution 2.07Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

CRYSTAL STRUCTURE OF HUMAN ALPHA THROMBIN IN COMPLEX WITH 5-AMIDINOINDOLE-4-BENZYLPIPERIDINE INHIBITOR

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The crystal structure of human alpha-thrombin in complex with LY178550, a, nonpeptidyl, active site-directed inhibitor, has been solved to 2.07 A, resolution by the method of X-ray crystallography. The final model of the, complex has a crystallographic R-value of 21.5% (Rfree = 23.1%) with 0.014, A and 2.4 degrees standard deviation from ideal bond lengths and angles, respectively. Well-defined electron density was observed for the inhibitor, in the active site. The inhibitor binds to the active site in an L-shaped, manner, mimicking the bound conformation of the tripeptide arginal series, of thrombin inhibitors (Chirgadze NY et al., 1992, American, Crystallographic Association Meeting 20: 116 [Abstr. PB311]). The basic, amidine of LY178550 forms a salt bridge with Asp 189 within the, specificity pocket, while the 4-benzylpiperidine side chain engages in a, number of hydrophobic interactions at the S2 and S3 binding sites. The, inhibitor does not interact in any fashion with the active site sequence, Ser 214-Gly 216, as occurs with many of the inhibitors studied previously., The indole N-H of the inhibitor forms a hydrogen bond to the gamma-oxygen, of the catalytic serine (Ser 195).

Disease

Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]

About this Structure

1D4P is a Protein complex structure of sequences from Hirudo medicinalis and Homo sapiens with , and as ligands. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.

Reference

The crystal structure of human alpha-thrombin complexed with LY178550, a nonpeptidyl, active site-directed inhibitor., Chirgadze NY, Sall DJ, Klimkowski VJ, Clawson DK, Briggs SL, Hermann R, Smith GF, Gifford-Moore DS, Wery JP, Protein Sci. 1997 Jul;6(7):1412-7. PMID:9232642

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