|PROSITE documentation PDOC00064|
Hydroxymethylglutaryl-coenzyme A reductase (EC 126.96.36.199) (HMG-CoA reductase) [1,2] catalyzes the NADP-dependent synthesis of mevalonate from 3-hydroxy-3-methylglutaryl-CoA. In vertebrates, HMG-CoA reductase is the rate-limiting enzyme in cholesterol biosynthesis. In plants, mevalonate is the precursor of all isoprenoid compounds.
HMG-CoA reductase is a membrane bound enzyme. Structurally, it consists of 3 domains. An N-terminal region that contains a variable number of transmembrane segments (7 in mammals, insects and fungi; 2 in plants), a linker region and a C-terminal catalytic domain of approximately 400 amino-acid residues.
In archebacteria  HMG-CoA reductase, which is involved in the biosynthesis of the isoprenoids side chains of lipids, seems to be cytoplasmic and lack the N-terminal hydrophobic domain.
Some bacteria, such as Pseudomonas mevalonii, can use mevalonate as the sole carbon source. These bacteria use an NAD-dependent HMG-CoA reductase (EC 188.8.131.52) to deacetylate mevalonate into 3-hydroxy-3-methylglutaryl-CoA . The Pseudomonas enzyme is structurally related to the catalytic domain of NADP-dependent HMG-CoA reductases.
We selected three conserved regions as signature patterns for HMG-CoA reductases. The first is located in the center of the catalytic domain, the second is a glycine-rich region located in the C-terminal section of the same catalytic domain and the third is also located in the C-terminal section and contains an histidine residue that seems  to be implicated in the catalytic mechanism as a general base.Last update:
April 2006 / Pattern revised.
PROSITE methods (with tools and information) covered by this documentation:
|1||Authors||Caelles C. Ferrer A. Balcells L. Hegardt F.G. Boronat A.|
|Title||Isolation and structural characterization of a cDNA encoding Arabidopsis thaliana 3-hydroxy-3-methylglutaryl coenzyme A reductase.|
|Source||Plant Mol. Biol. 13:627-638(1989).|
|2||Authors||Basson M.E. Thorsness M. Finer-Moore J. Stroud R.M. Rine J.|
|Title||Structural and functional conservation between yeast and human 3-hydroxy-3-methylglutaryl coenzyme A reductases, the rate-limiting enzyme of sterol biosynthesis.|
|Source||Mol. Cell. Biol. 8:3797-3808(1988).|
|3||Authors||Lam W.L. Doolittle W.F.|
|Title||Mevinolin-resistant mutations identify a promoter and the gene for a eukaryote-like 3-hydroxy-3-methylglutaryl-coenzyme A reductase in the archaebacterium Haloferax volcanii.|
|Source||J. Biol. Chem. 267:5829-5834(1992).|
|4||Authors||Beach M.J. Rodwell V.W.|
|Title||Cloning, sequencing, and overexpression of mvaA, which encodes Pseudomonas mevalonii 3-hydroxy-3-methylglutaryl coenzyme A reductase.|
|Source||J. Bacteriol. 171:2994-3001(1989).|
|5||Authors||Darnay B.G. Wang Y. Rodwell V.W.|
|Title||Identification of the catalytically important histidine of 3-hydroxy-3-methylglutaryl-coenzyme A reductase.|
|Source||J. Biol. Chem. 267:15064-15070(1992).|