2F9A

HMG-CoA synthase from Brassica juncea in complex with F-244

Summary for 2F9A

• Entry DOI: 10.2210/pdb2f9a/pdb
• Related: 2F82 2FA0 2FA3
• Descriptor: 3-Hydroxy-3-methylglutaryl coenzyme A synthase 1, (7R,12R,13R)-13-formyl-12,14-dihydroxy-3,5,7-trimethyltetradeca-2,4-dienoic acid (3 entities in total)
• Functional Keywords: hmgs1, f-244, transferase
• Biological source: Brassica juncea
• Total number of polymer chains: 1
• Total formula weight: 50352.26

Authors

Pojer, F.,Ferrer, J.L.,Richard, S.B.,Noel, J.P. (deposition date: 2005-12-05, release date: 2006-07-25, Last modification date: 2024-10-09)

Primary citation

Pojer, F.,Ferrer, J.L.,Richard, S.B.,Nagegowda, D.A.,Chye, M.L.,Bach, T.J.,Noel, J.P.
Structural basis for the design of potent and species-specific inhibitors of 3-hydroxy-3-methylglutaryl CoA synthases.
Proc.Natl.Acad.Sci.Usa, 103:11491-11496, 2006

PubMed Abstract: 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-undecadienenoic 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.

PubMed: 16864776
DOI: 10.1073/pnas.0604935103

Experimental method

X-RAY DIFFRACTION (2.51 Å)