2bxv

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Revision as of 18:18, 29 October 2007

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spinqualitylabelsall models 2bxv, resolution 2.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

DUAL BINDING MODE OF A NOVEL SERIES OF DHODH INHIBITORS

Overview

Human dihydroorotate dehydrogenase (DHODH) represents an important target, for the treatment of hyperproliferative and inflammatory diseases. In the, cell DHODH catalyzes the rate-limiting step of the de novo pyrimidine, biosynthesis. DHODH inhibition results in beneficial immunosuppressant and, antiproliferative effects in diseases such as rheumatoid arthritis. Here, we present high-resolution X-ray structures of human DHODH in complex with, a novel class of low molecular weight compounds that inhibit the enzyme in, the nanomolar range. Some compounds showed an interesting dual binding, mode within the same cocrystal strongly depending on the nature of, chemical substitution. Measured in vitro activity data correlated with the, prevailing mode of binding and explained the observed ... [(full description)]

About this Structure

2BXV is a [Single protein] structure of sequence from [Homo sapiens] with SO4, ACT, FMN, ORO and 3FT as [ligands]. Active as [[1]], with EC number [1.3.3.1]. Full crystallographic information is available from [OCA].

Reference

Dual binding mode of a novel series of DHODH inhibitors., Baumgartner R, Walloschek M, Kralik M, Gotschlich A, Tasler S, Mies J, Leban J, J Med Chem. 2006 Feb 23;49(4):1239-47. PMID:16480261

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