PROSITE documentation PDOC00064
Hydroxymethylglutaryl-coenzyme A reductase signatures and profile


Hydroxymethylglutaryl-coenzyme A reductase (EC (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 [3] 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 to deacetylate mevalonate into 3-hydroxy-3-methylglutaryl-CoA [3]. 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 [4] to be implicated in the catalytic mechanism as a general base.

Last update:

April 2006 / Pattern revised.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

HMG_COA_REDUCTASE_4, PS50065; Hydroxymethylglutaryl-coenzyme A reductases family profile  (MATRIX)

HMG_COA_REDUCTASE_1, PS00066; Hydroxymethylglutaryl-coenzyme A reductases signature 1  (PATTERN)

HMG_COA_REDUCTASE_2, PS00318; Hydroxymethylglutaryl-coenzyme A reductases signature 2  (PATTERN)

HMG_COA_REDUCTASE_3, PS01192; Hydroxymethylglutaryl-coenzyme A reductases signature 3  (PATTERN)


1AuthorsCaelles C. Ferrer A. Balcells L. Hegardt F.G. Boronat A.
TitleIsolation and structural characterization of a cDNA encoding Arabidopsis thaliana 3-hydroxy-3-methylglutaryl coenzyme A reductase.
SourcePlant Mol. Biol. 13:627-638(1989).
PubMed ID2491679

2AuthorsBasson M.E. Thorsness M. Finer-Moore J. Stroud R.M. Rine J.
TitleStructural and functional conservation between yeast and human 3-hydroxy-3-methylglutaryl coenzyme A reductases, the rate-limiting enzyme of sterol biosynthesis.
SourceMol. Cell. Biol. 8:3797-3808(1988).
PubMed ID3065625

3AuthorsLam W.L. Doolittle W.F.
TitleMevinolin-resistant mutations identify a promoter and the gene for a eukaryote-like 3-hydroxy-3-methylglutaryl-coenzyme A reductase in the archaebacterium Haloferax volcanii.
SourceJ. Biol. Chem. 267:5829-5834(1992).
PubMed ID1556098

4AuthorsBeach M.J. Rodwell V.W.
TitleCloning, sequencing, and overexpression of mvaA, which encodes Pseudomonas mevalonii 3-hydroxy-3-methylglutaryl coenzyme A reductase.
SourceJ. Bacteriol. 171:2994-3001(1989).
PubMed ID2656635

5AuthorsDarnay B.G. Wang Y. Rodwell V.W.
TitleIdentification of the catalytically important histidine of 3-hydroxy-3-methylglutaryl-coenzyme A reductase.
SourceJ. Biol. Chem. 267:15064-15070(1992).
PubMed ID1634543

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