DB code: M00180

RLCP classification 9.5010.584100.976 : Hydride transfer
5.501.400060.67 : Elimination
9.5010.536000.976 : Hydride transfer
CATH domain -.-.-.- :
1.10.3270.10 : HMGR, N-terminal domain
3.90.770.10 : 3-hydroxy-3-methylglutaryl-coenzyme A Reductase; Chain A, domain 2 Catalytic domain
3.30.70.420 : Alpha-Beta Plaits Catalytic domain
E.C. 1.1.1.34
CSA 1dqa
M-CSA 1dqa
MACiE M0093

CATH domain Related DB codes (homologues)
3.30.70.420 : Alpha-Beta Plaits D00607
3.90.770.10 : 3-hydroxy-3-methylglutaryl-coenzyme A Reductase; Chain A, domain 2 D00607

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P04035 3-hydroxy-3-methylglutaryl-coenzyme A reductase
HMG-CoA reductase
EC 1.1.1.34
NP_000850.1 (Protein)
NM_000859.2 (DNA/RNA sequence)
NP_001124468.1 (Protein)
NM_001130996.1 (DNA/RNA sequence)
PF00368 (HMG-CoA_red)
[Graphical View]

KEGG enzyme name
hydroxymethylglutaryl-CoA reductase (NADPH)
hydroxymethylglutaryl coenzyme A reductase (reduced nicotinamideadenine dinucleotide phosphate)
3-hydroxy-3-methylglutaryl-CoA reductase
beta-hydroxy-beta-methylglutaryl coenzyme A reductase
hydroxymethylglutaryl CoA reductase (NADPH)
S-3-hydroxy-3-methylglutaryl-CoA reductase
NADPH-hydroxymethylglutaryl-CoA reductase
HMGCoA reductase-mevalonate:NADP-oxidoreductase (acetylating-CoA)
3-hydroxy-3-methylglutaryl CoA reductase (NADPH)
hydroxymethylglutaryl-CoA reductase (NADPH2)

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P04035 HMDH_HUMAN (R)-mevalonate + CoA + 2 NADP(+) = (S)-3- hydroxy-3-methylglutaryl-CoA + 2 NADPH. Homodimer. Endoplasmic reticulum membrane, Multi-pass membrane protein. Peroxisome membrane, Multi-pass membrane protein.

KEGG Pathways
Map code Pathways E.C.
MAP00100 Biosynthesis of steroids

Compound table
Substrates Products Intermediates
KEGG-id C00356 C00005 C00080 C00418 C00010 C00006 I00101 I00102
E.C.
Compound (S)-3-Hydroxy-3-methylglutaryl-CoA NADPH H+ (R)-Mevalonate CoA NADP+ Mevaldyl-CoA Mevaldehyde
Type amine group,carbohydrate,carboxyl group,nucleotide ,peptide/protein,sulfide group amide group,amine group,nucleotide others carbohydrate,carboxyl group amine group,carbohydrate,nucleotide ,peptide/protein,sulfhydryl group amide group,amine group,nucleotide
ChEBI 15467
16474
15378
17710
15346
18009
PubChem 439218
445127
5884
1038
439230
6816
87642
5886
1dq8A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dq8B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dq8C01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dq8D01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dq9A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dq9B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dq9C01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dq9D01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dqaA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dqaB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dqaC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dqaD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hw8A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hw8B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hw8C01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hw8D01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hw9A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hw9B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hw9C01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hw9D01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hwiA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hwiB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hwiC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hwiD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hwjA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hwjB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hwjC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hwjD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hwkA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hwkB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hwkC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hwkD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hwlA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hwlB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hwlC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hwlD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dq8A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:COA Unbound Unbound Unbound
1dq8B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:COA Unbound Unbound Intermediate-analogue:MAH
1dq8C02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:COA Unbound Unbound Intermediate-analogue:MAH
1dq8D02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:COA Unbound Unbound Intermediate-analogue:MAH
1dq9A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:HMG Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:MAH
1dq9B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:HMG Unbound Unbound Unbound Unbound Unbound Unbound
1dq9C02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:HMG Unbound Unbound Unbound Unbound Unbound Unbound
1dq9D02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:HMG Unbound Unbound Unbound Unbound Unbound Unbound
1dqaA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:COA Unbound Unbound Unbound
1dqaB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:COA Unbound Unbound Intermediate-analogue:MAH
1dqaC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:COA Unbound Unbound Intermediate-analogue:MAH
1dqaD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:COA Unbound Unbound Intermediate-analogue:MAH
1hw8A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:114 Intermediate-analogue:MAH
1hw8B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Analogue:ADP Unbound Intermediate-analogue:114 Unbound
1hw8C02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:114 Unbound
1hw8D02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:114 Unbound
1hw9A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Analogue:ADP Unbound Intermediate-analogue:SIM Unbound
1hw9B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Analogue:ADP Unbound Intermediate-analogue:SIM Unbound
1hw9C02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:SIM Unbound
1hw9D02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Analogue:ADP Unbound Intermediate-analogue:SIM Unbound
1hwiA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Analogue:ADP Unbound Intermediate-analogue:115 Unbound
1hwiB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:115 Unbound
1hwiC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:115 Unbound
1hwiD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:115 Unbound
1hwjA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Analogue:ADP Unbound Intermediate-analogue:116 Unbound
1hwjB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Analogue:ADP Unbound Intermediate-analogue:116 Unbound
1hwjC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:116 Unbound
1hwjD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Analogue:ADP Unbound Intermediate-analogue:116 Unbound
1hwkA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Analogue:ADP Unbound Intermediate-analogue:117 Unbound
1hwkB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Analogue:ADP Unbound Intermediate-analogue:117 Unbound
1hwkC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:117 Unbound
1hwkD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:117 Unbound
1hwlA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Analogue:ADP Unbound Intermediate-analogue:FBI Unbound
1hwlB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Analogue:ADP Unbound Intermediate-analogue:FBI Unbound
1hwlC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:FBI Unbound
1hwlD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Analogue:ADP Unbound Intermediate-analogue:FBI Unbound
1dq8A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dq8B03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dq8C03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dq8D03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dq9A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dq9B03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dq9C03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dq9D03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dqaA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Bound:NAP Unbound Unbound
1dqaB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Bound:NAP Unbound Unbound
1dqaC03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Bound:NAP Unbound Unbound
1dqaD03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Bound:NAP Unbound Unbound
1hw8A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hw8B03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hw8C03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hw8D03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Analogue:ADP Unbound Unbound
1hw9A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hw9B03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Analogue:ADP Unbound Unbound
1hw9C03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hw9D03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Analogue:ADP Unbound Unbound
1hwiA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hwiB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Analogue:ADP Unbound Unbound
1hwiC03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hwiD03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Analogue:ADP Unbound Unbound
1hwjA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hwjB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Analogue:ADP Unbound Unbound
1hwjC03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Analogue:ADP Unbound Unbound
1hwjD03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Analogue:ADP Unbound Unbound
1hwkA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Analogue:ADP Unbound Unbound
1hwkB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Analogue:ADP Unbound Unbound
1hwkC03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hwkD03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Analogue:ADP Unbound Unbound
1hwlA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hwlB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hwlC03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hwlD03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P04035 & literature [19]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1dq8A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1dq8B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1dq8C01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1dq8D01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1dq9A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1dq9B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1dq9C01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1dq9D01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1dqaA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1dqaB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1dqaC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1dqaD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1hw8A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1hw8B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1hw8C01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1hw8D01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1hw9A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1hw9B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1hw9C01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1hw9D01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1hwiA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1hwiB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1hwiC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1hwiD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1hwjA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1hwjB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1hwjC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1hwjD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1hwkA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1hwkB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1hwkC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1hwkD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1hwlA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1hwlB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1hwlC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1hwlD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant M485I
1dq8A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1dq8B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1dq8C02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1dq8D02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1dq9A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1dq9B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1dq9C02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767;HIS 866
1dq9D02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1dqaA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767;HIS 866
1dqaB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767;HIS 866
1dqaC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767;HIS 866
1dqaD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767;HIS 866
1hw8A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1hw8B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1hw8C02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1hw8D02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1hw9A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1hw9B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1hw9C02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1hw9D02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1hwiA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1hwiB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1hwiC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1hwiD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1hwjA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1hwjB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1hwjC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1hwjD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1hwkA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1hwkB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1hwkC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1hwkD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1hwlA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1hwlB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1hwlC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1hwlD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 559;ASP 767; invisible H866
1dq8A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1dq8B03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1dq8C03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1dq8D03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1dq9A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1dq9B03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1dq9C03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1dq9D03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1dqaA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1dqaB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1dqaC03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1dqaD03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1hw8A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1hw8B03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1hw8C03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1hw8D03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1hw9A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1hw9B03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1hw9C03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1hw9D03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1hwiA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1hwiB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1hwiC03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1hwiD03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1hwjA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1hwjB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1hwjC03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1hwjD03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1hwkA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1hwkB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1hwkC03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1hwkD03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1hwlA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1hwlB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1hwlC03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691
1hwlD03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 691

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[8]
Fig.1
[13]
Fig.7, p.11481-11482
[15]
Fig.8, p.16865-16866
[17]
Scheme 1, Scheme 2
[19]
Fig. 1, Fig. 5, p.14-16
[20]
p.826-827

References
[1]
Resource
Comments
Medline ID
PubMed ID 6247408
Journal J Lipid Res
Year 1980
Volume 21
Pages 399-405
Authors Hunter CF, Rodwell VW
Title Regulation of vertebrate liver HMG-CoA reductase via reversible modulation of its catalytic activity.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 2991281
Journal J Biol Chem
Year 1985
Volume 260
Pages 10271-7
Authors Luskey KL, Stevens B
Title Human 3-hydroxy-3-methylglutaryl coenzyme A reductase. Conserved domains responsible for catalytic activity and sterol-regulated degradation.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 3058035
Journal Arch Biochem Biophys
Year 1988
Volume 267
Pages 110-8
Authors Mayer RJ, Debouck C, Metcalf BW
Title Purification and properties of the catalytic domain of human 3-hydroxy-3-methylglutaryl-CoA reductase expressed in Escherichia coli.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 3065625
Journal Mol Cell Biol
Year 1988
Volume 8
Pages 3797-808
Authors Basson ME, Thorsness M, Finer-Moore J, Stroud RM, 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.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 2491679
Journal Plant Mol Biol
Year 1989
Volume 13
Pages 627-38
Authors Caelles C, Ferrer A, Balcells L, Hegardt FG, Boronat A
Title Isolation and structural characterization of a cDNA encoding Arabidopsis thaliana 3-hydroxy-3-methylglutaryl coenzyme A reductase.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 2813388
Journal Proc Natl Acad Sci U S A
Year 1989
Volume 86
Pages 8217-21
Authors Rajkovic A, Simonsen JN, Davis RE, Rottman FM
Title Molecular cloning and sequence analysis of 3-hydroxy-3-methylglutaryl-coenzyme A reductase from the human parasite Schistosoma mansoni.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 2369897
Journal EMBO J
Year 1990
Volume 9
Pages 2439-46
Authors Clarke PR, Hardie DG
Title Regulation of HMG-CoA reductase: identification of the site phosphorylated by the AMP-activated protein kinase in vitro and in intact rat liver.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 2123872
Journal J Biol Chem
Year 1990
Volume 265
Pages 21634-41
Authors Wang Y, Darnay BG, Rodwell VW
Title Identification of the principal catalytically important acidic residue of 3-hydroxy-3-methylglutaryl coenzyme A reductase.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 1685759
Journal Lipids
Year 1991
Volume 26
Pages 637-48
Authors Bach TJ, Boronat A, Caelles C, Ferrer A, Weber T, Wettstein A
Title Aspects related to mevalonate biosynthesis in plants.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 8374303
Journal Protein Expr Purif
Year 1993
Volume 4
Pages 337-44
Authors Frimpong K, Darnay BG, Rodwell VW
Title Syrian hamster 3-hydroxy-3-methylglutaryl-coenzyme A reductase expressed in Escherichia coli: production of homogeneous protein.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 8112324
Journal Eur J Biochem
Year 1994
Volume 219
Pages 743-50
Authors Ball KL, Dale S, Weekes J, Hardie DG
Title Biochemical characterization of two forms of 3-hydroxy-3-methylglutaryl-CoA reductase kinase from cauliflower (Brassica oleracia).
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 8288583
Journal J Biol Chem
Year 1994
Volume 269
Pages 1217-21
Authors Frimpong K, Rodwell VW
Title The active site of hamster 3-hydroxy-3-methylglutaryl-CoA reductase resides at the subunit interface and incorporates catalytically essential acidic residues from separate polypeptides.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 7908908
Journal J Biol Chem
Year 1994
Volume 269
Pages 11478-83
Authors Frimpong K, Rodwell VW
Title Catalysis by Syrian hamster 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Proposed roles of histidine 865, glutamate 558, and aspartate 766.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 8120043
Journal J Biol Chem
Year 1994
Volume 269
Pages 6810-4
Authors Omkumar RV, Darnay BG, Rodwell VW
Title Modulation of Syrian hamster 3-hydroxy-3-methylglutaryl-CoA reductase activity by phosphorylation. Role of serine 871.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 8207009
Journal J Biol Chem
Year 1994
Volume 269
Pages 16862-6
Authors Omkumar RV, Rodwell VW
Title Phosphorylation of Ser871 impairs the function of His865 of Syrian hamster 3-hydroxy-3-methylglutaryl-CoA reductase.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 8302869
Journal Proc Natl Acad Sci U S A
Year 1994
Volume 91
Pages 927-31
Authors Enjuto M, Balcells L, Campos N, Caelles C, Arro M, Boronat A
Title Arabidopsis thaliana contains two differentially expressed 3-hydroxy-3-methylglutaryl-CoA reductase genes, which encode microsomal forms of the enzyme.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 10413460
Journal Biochemistry
Year 1999
Volume 38
Pages 8879-83
Authors Bochar DA, Tabernero L, Stauffacher CV, Rodwell VW
Title Aminoethylcysteine can replace the function of the essential active site lysine of Pseudomonas mevalonii 3-hydroxy-3-methylglutaryl coenzyme A reductase.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 9973353
Journal J Bacteriol
Year 1999
Volume 181
Pages 1256-63
Authors Takahashi S, Kuzuyama T, Seto H
Title Purification, characterization, and cloning of a eubacterial 3-hydroxy-3-methylglutaryl coenzyme A reductase, a key enzyme involved in biosynthesis of terpenoids.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 11111074
Journal Biochim Biophys Acta
Year 2000
Volume 1529
Pages 9-18
Authors Istvan ES, Deisenhofer J
Title The structure of the catalytic portion of human HMG-CoA reductase.
Related PDB
Related UniProtKB
[20]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 422-888, AND SUBUNIT.
Medline ID
PubMed ID 10698924
Journal EMBO J
Year 2000
Volume 19
Pages 819-30
Authors Istvan ES, Palnitkar M, Buchanan SK, Deisenhofer J
Title Crystal structure of the catalytic portion of human HMG-CoA reductase: insights into regulation of activity and catalysis.
Related PDB 1dq8 1dq9 1dqa 1dq8 1dq9
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 11370859
Journal Mol Genet Genomics
Year 2001
Volume 265
Pages 135-42
Authors Kato-Emori S, Higashi K, Hosoya K, Kobayashi T, Ezura H
Title Cloning and characterization of the gene encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase in melon (Cucumis melo L. reticulatus).
Related PDB
Related UniProtKB
[22]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 11349148
Journal Science
Year 2001
Volume 292
Pages 1160-4
Authors Istvan ES, Deisenhofer J
Title Structural mechanism for statin inhibition of HMG-CoA reductase.
Related PDB 1hw8 1hw9 1hwi 1hwj 1hwk 1hwl
Related UniProtKB

Comments
This enzyme is composed of the N-terminal transmembrane domain, linker region, and the C-terminal catalytic domains. Tertiary structures have been solved for the C-terminal catalytic domains (see [7]).
HMG-CoA reductase from Pseudomonas mevalonii, which does not have transmembrane domain, is homologous to this enzyme (EC 1.1.1.88; D00607 in EzCatDB). The active site of this enzyme is similar to that of the counterpart enzyme, but slightly different. Therefor the catalytic reaction is also similar but slightly different from that of the homologous enzyme.
According to the literature [13], [19] and [20], this enzyme catalyzes the following reactions:
(A) Hydride transfer from NADPH to HMG-CoA, forming the first intermediate, Mevaldyl-CoA (I00101):
(A0) Asp767 may modulate the charge/activity of Glu559 and Lys691. (Asp767 raise the pKa of Glu559 so that it could be protonated.)
(A1) Hydride transfer occurs from nicotinamide group of NADPH to the carbonyl carbon of the substrate HMG-CoA. Simultaneously, Lys691 and the protonated Glu559 stabilizes the negative charge on the oxygen during the formation of Mevaldyl-CoA.
(B) Eliminative double-bond formation; Elimination of CoASH from Mevaldyl-CoA, forming the second intermediate, Mevaldehyde (I00102):
(B0) Asp767 may modulate the charge/activity of Glu559 and Lys691.
(B1) Glu559 and Lys691 stabilizes the negative charge on the oxygen atom of the intermediate.
(B2) His866 on the C-terminal movable domain acts as general acid to protonate the sulfur atom (or thioanion) of the eliminated group, CoA, to complete the reaction. This elimination reaction seems to be E1cB-like reaction.
(C) Hydride transfer from NADPH to Mevaldehyde, forming product, Mevalonate:
(C0) Asp767 may modulate the charge/activity of Glu559 and Lys691.
(C1) Lys691 acts as a general acid to protonate the carbonyl oxygen of Mevaldehyde. At the same time, hydride transfer occurs from nicotinamide group of NADH to the carbonyl carbon of Mevaldehyde.

Created Updated
2004-03-24 2011-09-05