Your browser version may not work well with NCBI's Web applications. More information here...
1: Science. 1995 Jun 23;268(5218):1758-62.
Related Articles, Links
Click here to read
Crystal structure of Pseudomonas mevalonii HMG-CoA reductase at 3.0 angstrom resolution.

Lawrence CM, Rodwell VW, Stauffacher CV.

Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.

The rate-limiting step in cholesterol biosynthesis in mammals is catalyzed by 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, a four-electron oxidoreductase that converts HMG-CoA to mevalonate. The crystal structure of HMG-CoA reductase from Pseudomonas mevalonii was determined at 3.0 angstrom resolution by multiple isomorphous replacement. The structure reveals a tightly bound dimer that brings together at the subunit interface the conserved residues implicated in substrate binding and catalysis. These dimers are packed about a threefold crystallographic axis, forming a hexamer with 23 point group symmetry. Difference Fourier studies reveal the binding sites for the substrates HMG-CoA and reduced or oxidized nicotinamide adenine dinucleotide [NAD(H)] and demonstrate that the active sites are at the dimer interfaces. The HMG-CoA is bound by a domain with an unusual fold, consisting of a central alpha helix surrounded by a triangular set of walls of beta sheets and alpha helices. The NAD(H) is bound by a domain characterized by an antiparallel beta structure that defines a class of dinucleotide-binding domains.

Publication Types:
PMID: 7792601 [PubMed - indexed for MEDLINE]