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2f82

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Revision as of 15:18, 21 February 2008 by OCA (Talk | contribs)
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2f82, resolution 2.10Å

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HMG-CoA synthase from Brassica juncea in the apo-form

Overview

3-Hydroxy-3-methylglutaryl CoA synthase (HMGS) catalyzes the first committed step in the mevalonate metabolic pathway for isoprenoid biosynthesis and serves as an alternative target for cholesterol-lowering and antibiotic drugs. We have determined a previously undescribed crystal structure of a eukaryotic HMGS bound covalently to a potent and specific inhibitor F-244 [(E,E)-11-[3-(hydroxymethyl)-4-oxo-2-oxytanyl]-3,5,7-trimethyl-2,4-undecad ienenoic acid]. Given the accessibility of synthetic analogs of the F-244 natural product, this inhibited eukaryotic HMGS structure serves as a necessary starting point for structure-based methods that may improve the potency and species-specific selectivity of the next generation of F-244 analogs designed to target particular eukaryotic and prokaryotic HMGS.

About this Structure

2F82 is a Single protein structure of sequence from Brassica juncea. Full crystallographic information is available from OCA.

Reference

Structural basis for the design of potent and species-specific inhibitors of 3-hydroxy-3-methylglutaryl CoA synthases., Pojer F, Ferrer JL, Richard SB, Nagegowda DA, Chye ML, Bach TJ, Noel JP, Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11491-6. Epub 2006 Jul 24. PMID:16864776

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