{PDOC00064}
{PS00066; HMG_COA_REDUCTASE_1}
{PS00318; HMG_COA_REDUCTASE_2}
{PS01192; HMG_COA_REDUCTASE_3}
{PS50065; HMG_COA_REDUCTASE_4}
{BEGIN}
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* Hydroxymethylglutaryl-coenzyme A reductase signatures and profile *
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Hydroxymethylglutaryl-coenzyme A reductase  (EC 1.1.1.34)  (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 1.1.1.88)  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.

-Consensus pattern: [RKH]-x-{Y}-{I}-x-{I}-{L}-D-x-M-G-x-N-x-[LIVMA]
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: 4.

-Consensus pattern: [LIVM]-G-x-[LIVM]-G-G-[AG]-T
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: 6.

-Consensus pattern: A-[LIVM]-x-[STAN]-x(2)-[LI]-x-[KRNQ]-[GSA]-H-[LM]-x-
                    [FYLH]
                    [H is an active site residue]
-Sequences known to belong to this class detected by the pattern: ALL,  except
 for archaebacterial HMG-CoA reductases.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: April 2006 / Pattern revised.

[ 1] Caelles C., Ferrer A., Balcells L., Hegardt F.G., Boronat A.
     "Isolation and structural characterization of a cDNA encoding
     Arabidopsis thaliana 3-hydroxy-3-methylglutaryl coenzyme A
     reductase."
     Plant Mol. Biol. 13:627-638(1989).
     PubMed=2491679
[ 2] Basson M.E., Thorsness M., Finer-Moore J., Stroud R.M., Rine J.
     "Structural and functional conservation between yeast and human
     3-hydroxy-3-methylglutaryl coenzyme A reductases, the rate-limiting
     enzyme of sterol biosynthesis."
     Mol. Cell. Biol. 8:3797-3808(1988).
     PubMed=3065625
[ 3] Lam W.L., Doolittle W.F.
     "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."
     J. Biol. Chem. 267:5829-5834(1992).
     PubMed=1556098
[ 4] Beach M.J., Rodwell V.W.
     "Cloning, sequencing, and overexpression of mvaA, which encodes
     Pseudomonas mevalonii 3-hydroxy-3-methylglutaryl coenzyme A
     reductase."
     J. Bacteriol. 171:2994-3001(1989).
     PubMed=2656635
[ 5] Darnay B.G., Wang Y., Rodwell V.W.
     "Identification of the catalytically important histidine of
     3-hydroxy-3-methylglutaryl-coenzyme A reductase."
     J. Biol. Chem. 267:15064-15070(1992).
     PubMed=1634543

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