2ijn
From Proteopedia
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Isothiazoles as active-site inhibitors of HCV NS5B polymerase
Overview
Isothiazole analogs were discovered as a novel class of active-site inhibitors of HCV NS5B polymerase. The best compound has an IC(50) of 200 nM and EC(50) of 100 nM, which is a significant improvement over the starting inhibitor (1). The X-ray complex structure of 1 with HCV NS5B was obtained at a resolution of 2.2A, revealing that the inhibitor is covalently linked with Cys 366 of the 'primer-grip'. Furthermore, it makes considerable contacts with the C-terminus, beta-loop, and more importantly, to the active-site of the enzyme. The uniqueness of this binding mode offers a new insight for the rational design of novel inhibitors for HCV NS5B polymerase.
About this Structure
2IJN is a Single protein structure of sequence from Hepatitis c virus subtype 3b with as ligand. Active as RNA-directed RNA polymerase, with EC number 2.7.7.48 Full crystallographic information is available from OCA.
Reference
Isothiazoles as active-site inhibitors of HCV NS5B polymerase., Yan S, Appleby T, Gunic E, Shim JH, Tasu T, Kim H, Rong F, Chen H, Hamatake R, Wu JZ, Hong Z, Yao N, Bioorg Med Chem Lett. 2007 Jan 1;17(1):28-33. Epub 2006 Oct 5. PMID:17049853
Page seeded by OCA on Thu Feb 21 17:53:23 2008
