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Overview for MACiE Entry M0093

Version history

General Information

EC Number: 1.1.1.34 (A member of the Oxidoreductases, Acting on the CH-OH group of donors, With NAD+ or NADP+ as acceptor)

Enzyme Name: hydroxymethylglutaryl-CoA reductase (NADPH)

Biological Species: Homo sapiens (Human)

Catalytic Chain UniprotKB Accession Codes:

  • P04035 - 3-hydroxy-3-methylglutaryl-coenzyme A reductase

Representative PDB Code: 1dqa - COMPLEX OF THE CATALYTIC PORTION OF HUMAN HMG-COA REDUCTASEWITH HMG, COA, AND NADP+ (Resolution = 2.00 Å).

Catalytic CATH Codes:

  • 3.90.770.10 - 3-hydroxy-3-methylglutaryl-coenzyme A Reductase; Chain A, domain 2
  • 3.30.70.420 - Alpha-Beta Plaits

"Other" CATH Codes:

Display structure information

Overall Reaction:

Image of NADPH

Image of (S)-3-hydroxy-3-methylglutaryl-CoA

Image of proton

right arrow

Image of proton

Image of CoA

Image of NADP

Image of (R)-mevalonate

2 NADPH
C00005
CHEBI:16908
(S)-3-hydroxy-3-methylglutaryl-CoA
C00356
CHEBI:43074
2 proton
C00080
CHEBI:24636
proton
C00080
CHEBI:24636
CoA
C00010
CHEBI:57287
2 NADP
C00006
CHEBI:18009
(R)-mevalonate
C00418
CHEBI:36464

View similar reactions


Stepwise Description of the Reaction

Step 1NADP eliminates a hydride, which adds to the carbonyl carbon adjacent to the CoA moiety.
Step 2The oxyanion collapses, eliminating CoA, which deprotonates His866B.
Step 3A second molecule of NADP eliminates a hydride, which adds to the terminal carbonyl carbon, which deprotonates Glu559B.
Step 4Glu559B deprotonates water in an inferred return step.

View similar reactions (composite manual annotation)


Catalytic Residues Involved

Type Number Chain Location of Function
Lys 691 A Side Chain
Asp 767 A Side Chain
Glu 559 B Side Chain
His 866 B Side Chain

References

  1. E. S. Istvan et al. (2000), The EMBO Journal, 19, 819-830. Crystal structure of the catalytic portion of human HMG-CoA reductase: insights into regulation of activity and catalysis.
    Medline: 10698924
  2. E. S. Istvan et al. (2000), Biochim. Biophys. Acta, 1529, 9-18. The structure of the catalytic portion of human HMG-CoA reductase.
    Medline: 11111074

Homologue information for M0093 (1dqa)

CSA Homologues

MACiE Homologues (within the PDB)

MACiE Homologues (within UniprotKB/SwissProt)


Links to this entry in other databases

Link to EC-PDB-SUM Link to PDB-SUM Link to RCSB PDB Link to PDBe Link to CSA
Link to MetaCyc Link to KEGG Link to BRENDA Link to ExplorENZ
Link to EzCatDB

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hydroxymethylglutaryl-CoA reductase (NADPH) activity (molecular function)
peroxisome (cellular component)
peroxisomal membrane (cellular component)
endoplasmic reticulum (cellular component)
endoplasmic reticulum membrane (cellular component)
cholesterol biosynthetic process (biological process)
isoprenoid biosynthetic process (biological process)
germ cell migration (biological process)
gonad development (biological process)
coenzyme A metabolic process (biological process)
membrane (cellular component)
integral component of membrane (cellular component)
oxidoreductase activity (molecular function)
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor (molecular function)
NADP binding (molecular function)
coenzyme binding (molecular function)
oxidation-reduction process (biological process)
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