1z6j

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spinqualitylabelsall models 1z6j, resolution 2.0Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal Structure of a ternary complex of Factor VIIa/Tissue Factor/Pyrazinone Inhibitor

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

We describe the structure-based design, synthesis, and enzymatic activity, of a series of substituted pyrazinones as inhibitors of the TF/VIIa, complex. These inhibitors contain substituents meta to the P(1) amidine, designed to explore additional interactions with the VIIa residues in the, so-called 'S(1) side pocket'. A crystal structure of the designed, inhibitors demonstrates the ability of the P(1) side pocket moiety to, engage Lys192 and main chain of Gly216 via hydrogen bond interactions, thus, providing additional possibility for chemical modification to, improve selectivity and/or physical properties of inhibitors.

Disease

Known diseases associated with this structure: Esophageal squamous cell carcinoma OMIM:[606551], Factor VII deficiency OMIM:[227500], Myocardial infarction, decreased susceptibility to OMIM:[227500]

About this Structure

1Z6J is a Protein complex structure of sequences from Homo sapiens with CA, MG and PY3 as ligands. Active as Coagulation factor VIIa, with EC number 3.4.21.21 Full crystallographic information is available from OCA.

Reference

Structure-based design and synthesis of pyrazinones containing novel P1 'side pocket' moieties as inhibitors of TF/VIIa., Schweitzer BA, Neumann WL, Rahman HK, Kusturin CL, Sample KR, Poda GI, Kurumbail RG, Stevens AM, Stegeman RA, Stallings WC, South MS, Bioorg Med Chem Lett. 2005 Jun 15;15(12):3006-11. PMID:15913999

Page seeded by OCA on Mon Nov 12 20:29:58 2007