Information on EC 1.1.1.34 - hydroxymethylglutaryl-CoA reductase (NADPH)

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea

EC NUMBER
COMMENTARY
1.1.1.34
-
RECOMMENDED NAME
GeneOntology No.
hydroxymethylglutaryl-CoA reductase (NADPH)
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
(R)-mevalonate + CoA + 2 NADP+ = (S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
show the reaction diagram
-
-
-
-
(R)-mevalonate + CoA + 2 NADP+ = (S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
show the reaction diagram
via mevaldehyde as an intermediate product
-
(R)-mevalonate + CoA + 2 NADP+ = (S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
show the reaction diagram
Glu559 and His866 are involved in catalysis
-
(R)-mevalonate + CoA + 2 NADP+ = (S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
show the reaction diagram
via mevaldehyde as an intermediate product, enzyme contains a catalytic His381, Lys267 is also involved in catalysis, active site structure
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
Biosynthesis of secondary metabolites
-
isoprene biosynthesis II (engineered)
-
Metabolic pathways
-
mevalonate pathway I
-
mevalonate pathway II (archaea)
-
Terpenoid backbone biosynthesis
-
SYSTEMATIC NAME
IUBMB Comments
(R)-mevalonate:NADP+ oxidoreductase (CoA-acylating)
The enzyme is inactivated by EC 2.7.11.31 {[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase} and reactivated by EC 3.1.3.47 {[hydroxymethylglutaryl-CoA reductase (NADPH)]-phosphatase}.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
3-hydroxy-3-methyl-glutaryl CoA reductase
-
-
3-hydroxy-3-methylglutaryl Ccoenzyme A reductase 1
-
-
3-hydroxy-3-methylglutaryl co-enzyme A reductase
-
-
3-hydroxy-3-methylglutaryl CoA reductase
-
-
3-hydroxy-3-methylglutaryl CoA reductase
-
-
3-hydroxy-3-methylglutaryl CoA reductase
Q7YT62
-
3-hydroxy-3-methylglutaryl CoA reductase
-
-
3-hydroxy-3-methylglutaryl CoA reductase
-
-
3-hydroxy-3-methylglutaryl CoA reductase
-
-
3-hydroxy-3-methylglutaryl CoA reductase
-
-
3-hydroxy-3-methylglutaryl CoA reductase
-
-
3-hydroxy-3-methylglutaryl coenzyme A reductase
Q5RZ62
-
3-hydroxy-3-methylglutaryl coenzyme A reductase
-
-
3-hydroxy-3-methylglutaryl coenzyme A reductase
-
-
3-hydroxy-3-methylglutaryl coenzyme A reductase
Lactococcus lactis NZ9000
-
-
-
3-hydroxy-3-methylglutaryl coenzyme A reductase
-
-
3-hydroxy-3-methylglutaryl coenzyme A reductase 1
-
-
3-hydroxy-3-methylglutaryl-CoA reductase
-
-
-
-
3-hydroxy-3-methylglutaryl-CoA reductase
-
-
3-hydroxy-3-methylglutaryl-CoA reductase
-
-
3-hydroxy-3-methylglutaryl-CoA reductase (NADPH)
-
-
-
-
3-hydroxy-3-methylglutaryl-coenzyme A reductase
B2KX91
-
3-hydroxy-3-methylglutaryl-coenzyme A reductase
-
-
3-hydroxy-3-methylglutaryl-coenzyme A reductase
Q1W675
-
3-hydroxymethylglutaryl coenzyme A reductase
-
-
acetoacetyl-coenzyme A thiolase/3-hydroxy-3-methylglutaryl-coenzyme A reductase
-
-
beta-hydroxy-beta-methylglutaryl coenzyme A reductase
-
-
-
-
beta-hydroxy-beta-methylglutaryl-Co A reductase
-
-
-
-
EuHMGR
Q5RZ62
-
HMG CoA reductase
-
-
HMG-CoA reductase
-
-
-
-
HMG-CoA reductase
-
-
HMG-CoA reductase
Aureobasidium pullulans MZKI B802
-
-
-
HMG-CoA reductase
-
-
HMG-CoA reductase
-
-
HMG-CoA reductase
-
-
HMG-CoA reductase
Debaryomyces hansenii CBS 767
-
-
-
HMG-CoA reductase
A0N0D3
-
HMG-CoA reductase
-
-
HMG-CoA reductase
Eurotium amstelodami MZKI A561
-
-
-
HMG-CoA reductase
-
-
HMG-CoA reductase
-
-
HMG-CoA reductase
Hortaea werneckii MZKI B736
-
-
-
HMG-CoA reductase
-
-
HMG-CoA reductase
-
-
HMG-CoA reductase
-
-
HMG-CoA reductase
Phaeotheca triangularis MZKI B741
-
-
-
HMG-CoA reductase
Rattus norvegicus Sprague-Dawley
-
-
-
HMG-CoA reductase
-
-
HMG-CoA reductase
P12683
-
HMG-CoA reductase
Saccharomyces cerevisiae MZKI K86
-
-
-
HMG-CoA reductase
-
-
HMG-CoA reductase
Trimmatostroma salinum MZKI B734
-
-
-
HMG-CoA reductase
-
-
HMG-CoA reductase
Wallemia ichthyophaga EXF 994
-
-
-
HMG-CoAR
-
-
HMG-CoAR
-
-
HMG-CoAR
Rattus norvegicus Sprague-Dawley
-
-
-
HMG1
-
-
HMG2
-
-
HMG2.2
-
-
-
-
HMG3.3
-
-
-
-
HMGCoA reductase
-
-
HMGCoA reductase-mevalonate:NADP-oxidoreductase (acetylating CoA)
-
-
-
-
HMGCR
-
-
HMGR
-
-
-
-
HMGR
Aureobasidium pullulans MZKI B802
-
-
-
HMGR
Debaryomyces hansenii CBS 767
-
-
-
HMGR
Eurotium amstelodami MZKI A561
-
-
-
HMGR
B2KX91
-
HMGR
Q7YT62
-
HMGR
Hortaea werneckii MZKI B736
-
-
-
HMGR
Lactococcus lactis NZ9000
-
-
-
HMGR
-
-
HMGR
Mus musculus C57BL/6J
-
-
-
HMGR
Phaeotheca triangularis MZKI B741
-
-
-
HMGR
Saccharomyces cerevisiae MZKI K86
-
-
-
HMGR
Q1W675
-
HMGR
Trimmatostroma salinum MZKI B734
-
-
-
HMGR
Wallemia ichthyophaga EXF 994
-
-
-
HMGR1
-
-
-
-
HMGR1
Q7YT63
-
HMGR2
-
-
-
-
HMGR2
Q7YT63
-
hydroxy-3-methylglutoryl-Coenzyme A reductase
A0N0D3
-
hydroxymethylglutaryl CoA reductase (NADPH)
-
-
-
-
hydroxymethylglutaryl-coenzyme A reductase (reduced nicotinamide adenine dinucleotide phosphate)
-
-
-
-
mevalonate:NADP+ oxidoreductase (acetylating CoA)
-
-
-
-
microsomal HMG-CoA reductase
-
-
NADPH-hydroxymethylglutaryl-CoA reductase
-
-
-
-
S-3-hydroxy-3-methylglutaryl-CoA reductase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9028-35-7
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
2 genes hmg1 and hmg2 encode 2 isozymes HMG1 and HMG2
-
-
Manually annotated by BRENDA team
ecotype Columbia
-
-
Manually annotated by BRENDA team
Aureobasidium pullulans MZKI B802
MZKI B802
-
-
Manually annotated by BRENDA team
cauliflower
-
-
Manually annotated by BRENDA team
Debaryomyces hansenii CBS 767
CBS 767
-
-
Manually annotated by BRENDA team
dual-function enzyme with acetoacetyl-coenzyme A thiolase and 3-hydroxy-3-methylglutaryl-coenzyme A reductase activities
-
-
Manually annotated by BRENDA team
Oliver
SwissProt
Manually annotated by BRENDA team
Eurotium amstelodami MZKI A561
MZKI A561
-
-
Manually annotated by BRENDA team
a triterpene-producing fungus, strain HG
SwissProt
Manually annotated by BRENDA team
; gene hmgR
-
-
Manually annotated by BRENDA team
lobster, 2 enzyme forms: a soluble and a membrane-bound enzyme
SwissProt
Manually annotated by BRENDA team
lobster, 2 enzyme forms: a soluble isozyme HMGR1 and a membrane-bound isozyme HMGR2
SwissProt
Manually annotated by BRENDA team
MZKI B736
-
-
Manually annotated by BRENDA team
salt-tolerant black yeast, strain MZKI B736, isozymes Hmg1 and Hmg2
-
-
Manually annotated by BRENDA team
Hortaea werneckii MZKI B736
MZKI B736
-
-
Manually annotated by BRENDA team
cv. Norin 1
-
-
Manually annotated by BRENDA team
collected from Panzhihua, Sichuan province, China, gene hmgr
-
-
Manually annotated by BRENDA team
Lactococcus lactis NZ9000
-
-
-
Manually annotated by BRENDA team
genes LcHMG1 and LcHMG2
-
-
Manually annotated by BRENDA team
Syrian hamster
-
-
Manually annotated by BRENDA team
C57BL/6J mice
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6J
C57BL/6J mice
-
-
Manually annotated by BRENDA team
Phaeotheca triangularis MZKI B741
MZKI B741
-
-
Manually annotated by BRENDA team
class II enzyme
-
-
Manually annotated by BRENDA team
male Charles River Sprague-Dawley rats
-
-
Manually annotated by BRENDA team
Sprague-Dawley
-
-
Manually annotated by BRENDA team
young male Sprague-Dawley
Uniprot
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
Sprague-Dawley
-
-
Manually annotated by BRENDA team
Saccharomyces cerevisiae MZKI K86
MZKI K86
-
-
Manually annotated by BRENDA team
cv. Irish Cobbler
-
-
Manually annotated by BRENDA team
cv. Rishiri, interspecific hybrid
-
-
Manually annotated by BRENDA team
; enzyme is not regulated by phosphorylation
-
-
Manually annotated by BRENDA team
Trimmatostroma salinum MZKI B734
MZKI B734
-
-
Manually annotated by BRENDA team
Schizotrypanum
-
-
Manually annotated by BRENDA team
Wallemia ichthyophaga EXF 994
EXF 994
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
metabolism
-
part of cholesterol synthesis pathway
metabolism
-
HMGR catalyzes the first committed step in mevalonic acid pathway for biosynthesis of isoprenoids
metabolism
-
HMG-CoA reductase is the rate-limiting enzyme of cholesterol biosynthesis
metabolism
-
HMGR catalyzes the four-electron reduction of HMGCoA to mevalonate, the committed step in the biosynthesis of sterols. Mevalonate is a precursor of isoprenoids, a class of compounds involved in several cellular functions such as cholesterol synthesis and growth control
metabolism
-
3-hydroxy-3-methylglutaryl CoA reductase catalyzes the first committed step in the mevalonic acid (MVA) pathway for the biosynthesis of isoprenoids
metabolism
-
3-hydroxy-3-methylglutaryl Co-A reductase is a rate-limiting enzyme in the eukaryotic mevalonate pathway
physiological function
-
within cells, the concentration of mevalonate and therefore that of its metabolic products is tightly controlled through the activity of HMGR, an enzyme that catalyzes the four-electron reduction of 3-hydroxy-3-methylglutaryl-CoA to mevalonate
physiological function
-
the enzyme is the major regulatory enzyme of cholesterol biosynthesis and the target enzyme of many investigations aimed at lowering the rate of cholesterol biosynthesis
physiological function
Q1W675
rate-limiting enzyme for cholesterol synthesis, regulated via a negative feedback mechanism through sterols and non-sterol metabolites derived from mevalonate
physiological function
-
HMG1 is highly associated with the cell division during the early stage of fruit development which determines the final fruit size in Litchi chinensis. LcHMG2 is involved in the late stage of fruit development, in association with biosynthesis of isoprenoid compounds required for later cell enlargement
metabolism
Lactococcus lactis NZ9000
-
3-hydroxy-3-methylglutaryl Co-A reductase is a rate-limiting enzyme in the eukaryotic mevalonate pathway
-
additional information
-
modelling of the active site using crystal stucture of the enzyme with bound inhibitor simvastatin, PDB ID 1HW9, overview
additional information
Q1W675
structure-function analysis, overview. Identification of three characteristic sites of hydroxymethylglutaryl-CoA reductase
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(R)-mevalonate + CoA + 2 NADP+
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
show the reaction diagram
-
-
-
-
r
(R,S)-mevaldehyde + acetate
?
show the reaction diagram
-
-
-
-
?
(R,S)-mevaldehyde + NADPH
?
show the reaction diagram
-
-
-
-
?
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
(R)-mevalonate + 2 NADP+ + CoA
show the reaction diagram
-
-
-
-
-
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
(R)-mevalonate + 2 NADP+ + CoA
show the reaction diagram
-
-, HMGR is a key enzyme in the mevalonate pathway of isoprenoid biosynthesis, the sole route in haloarchaea for lipid and carotenoid production
-
-
?
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
(R)-mevalonate + CoA + 2 NADP+
show the reaction diagram
-
-
-
-
?
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
(R)-mevalonate + CoA + 2 NADP+
show the reaction diagram
-
-
-
-
?
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
(R)-mevalonate + CoA + 2 NADP+
show the reaction diagram
-
-
-
-
?
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
(R)-mevalonate + CoA + 2 NADP+
show the reaction diagram
Q1W675, -
-
-
-
?
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
(R)-mevalonate + CoA + 2 NADP+
show the reaction diagram
Lactococcus lactis NZ9000
-
-
-
-
?
(S)-3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
r
(S)-3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
r
(S)-3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
r
(S)-3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
r
(S)-3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
(S)-3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
r
(S)-3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-, Q7YT62, Q7YT63
-
-
-
r
(S)-3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
r
(S)-3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
enzyme is essential for sterol biosynthesis
-
-
r
(S)-3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
involved in isopentenyl diphosphate biosynthesis, mevalonate pathway overview, overall reaction
-
-
r
(S)-3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
overall reaction
-
-
r
(S)-3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
the reduction of 3-hydroxy-3-methylglutaryl-CoA is preferred over oxidation of mevalonate
-
-
r
(S)-3-hydroxy-3-methylglutaryl-CoA + NADPH
mevaldyl-CoA + NADP+
show the reaction diagram
-
first step reaction
-
-
?
(S)-3-hydroxy-3-methylglutaryl-CoA + NADPH
mevaldyl-CoA + NADP+
show the reaction diagram
-
first step reaction
-
-
r
(S)-3-hydroxy-3-methylglutaryl-CoA + NADPH
mevaldehyde + CoA + NADP+
show the reaction diagram
-
first step reaction
-
-
r
3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
mevalonolactone + CoA + 2 NADP+ + H2O
show the reaction diagram
-
-, rate-limiting step of cholesterol biosynthesis
-
-
r
3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
mevalonate + CoA + 2 NADP+
show the reaction diagram
-
-
-
-
r
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
r
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
-
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
-
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
ir
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
r
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
-
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?, r
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
r
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
first step reaction
-
-
r
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
substrate is (S)-isomer of HMG-CoA
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
Rattus norvegicus Wistar
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
mevalonate + CoA + NADP+
show the reaction diagram
P04035
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
mevalonate + CoA + NADP+
show the reaction diagram
-
up- and down-regulation of HMGR activity in response to changes in the flux of the mevalonate pathway occur via post-translational control
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH + H+
mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
acetyl-CoA
acetoacetyl-CoA + CoA
show the reaction diagram
-
-
-
-
r
D-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
(R)-mevalonate + CoA + 2 NADP+
show the reaction diagram
-
-
-
-
r
D-3-hydroxy-3-methylglutaryl-CoA + NADPH
mevalonate + CoA + NADP+
show the reaction diagram
Saccharomyces cerevisiae, Eurotium amstelodami, Aureobasidium pullulans, Debaryomyces hansenii, Hortaea werneckii, Phaeotheca triangularis, Trimmatostroma salinum, Wallemia ichthyophaga, Saccharomyces cerevisiae MZKI K86, Wallemia ichthyophaga EXF 994, Aureobasidium pullulans MZKI B802, Hortaea werneckii MZKI B736, Eurotium amstelodami MZKI A561, Phaeotheca triangularis MZKI B741, Debaryomyces hansenii CBS 767, Trimmatostroma salinum MZKI B734
-
-
-
-
?
DL-3-hydroxy-3-methylglutaryl-CoA + NADPH
mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
hydroxymethylglutaryl-CoA + NADPH + H+
mevalonate + NADP+ + CoA
show the reaction diagram
-
-
-
-
?
hydroxymethylglutaryl-CoA + NADPH + H+
mevalonate + NADP+ + CoA
show the reaction diagram
-
-
-
-
?
hydroxymethylglutaryl-CoA + NADPH + H+
mevalonate + NADP+ + CoA
show the reaction diagram
-
-
-
-
?
hydroxymethylglutaryl-CoA + NADPH + H+
mevalonate + NADP+ + CoA
show the reaction diagram
B2KX91, -
-
-
-
?
hydroxymethylglutaryl-CoA + NADPH + H+
mevalonate + NADP+ + CoA
show the reaction diagram
-
HMGR is the key regulatory enzyme of the mevalonate pathway and also the iridoid biosynthesis, it is highly regulated itself, HMGR may represent a regulator in maintenance of homeostasis between de novo produced and sequestered intermediates of iridoid metabolism, overview
-
-
?
hydroxymethylglutaryl-CoA + NADPH + H+
mevalonate + NADP+ + CoA
show the reaction diagram
-
key enzyme of the mevalonic acid pathway catalysing the first committed step with NADPH as cofactor, overview
-
-
?
hydroxymethylglutaryl-CoA + NADPH + H+
mevalonate + NADP+ + CoA
show the reaction diagram
-
the enzyme utilizes two molecules of NADPH to mediate the four-electron reduction of HMG-CoA to the carboxylic acid mevalonate, homology modeling of the catalytic domain
-
-
?
hydroxymethylglutaryl-CoA + NADPH + H+
mevalonate + NADP+ + CoA
show the reaction diagram
Mus musculus C57BL/6J
-
-
-
-
?
mevaldehyde + NADPH
(R)-mevalonate + NADP+
show the reaction diagram
-
-
-
-
?
mevaldehyde + NADPH
(R)-mevalonate + NADP+
show the reaction diagram
-
second step reaction
-
-
r
mevaldehyde + NADPH
(R)-mevalonate + NADP+
show the reaction diagram
-
third step reaction
-
-
r
mevaldehyde + NADPH + H+
(R)-mevalonate + NADP+
show the reaction diagram
-
-
-
-
?
mevaldyl-CoA + H2O
mevaldehyde + NADP+
show the reaction diagram
-
second step reaction
-
-
r
mevaldyl-CoA + NADPH + H+ + H2O
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
second step reaction
-
-
?
additional information
?
-
-
enzyme plays a central role in sterol biosynthesis, investigation of the physiological regulation, 3-hydroxy-3-methylglutaryl CoA reductase and C24-sterol methyltransferase type 1 work in concert to control carbon flux into end-product sterols
-
-
-
additional information
?
-
-
enzyme undergoes endoplasmic reticulum-associated degradation which is physiologically regulated by sterol pathway signals, determination of structural features leading to modification and degradation by the quality control system of the endoplasmic reticulum, overview
-
-
-
additional information
?
-
-
phytosterol biosynthetic pathway, overview
-
-
-
additional information
?
-
-
the reaction is a highly regulated process within the cholesterol biosynthetic pathway
-
-
-
additional information
?
-
-
rate-limiting enzyme in the biosynthesis of cholesterol in mammals
-
-
-
additional information
?
-
-
HMG-CoA reductase is regulated by salinity at the level of transcription
-
-
-
additional information
?
-
-
small heterodimer partner nuclear receptor directly regulates cholesterol biosynthesis through inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase
-
-
-
additional information
?
-
-
no substrate: NADH
-
-
-
additional information
?
-
-
biphasic regulation of HMG-CoA reductase expression and activity during wound healing and its functional role in the control of keratinocyte angiogenic and proliferative responses, overview
-
-
-
additional information
?
-
-
HMGR activity is not only diminished in iridoid producers but most likely prevalent within the Chrysomelina subtribe and also within the insecta
-
-
-
additional information
?
-
-
the expression of HMGR is regulated in response to non-optimal salinity in the halophilic archaeon
-
-
-
additional information
?
-
-
ubiquitination and proteasomal degradation of microsomal, but not mitochondrial, HMGR isozymes depends on environmental salinity, overview
-
-
-
additional information
?
-
A0N0D3, -
HMGR can accelerate the biosynthesis of carotenoids in the Escherichia coli transformant, it plays an influential role in isoprenoid biosynthesis
-
-
-
additional information
?
-
P12683
enzyme in the pathway for production of prenyl alcohols. Almost all Saccharomyces cerevisiae strains tend to produce mainly squalene and low amount of prenyl alcohols. Among these ATCC strains, relatively large amounts of prenyl alcohols in the cultures of two recombinants (ATCC201741 and ATCC 200027). Amounts are quite low compared to the case of ATCC 200589 recombinant. These differences possibly depend on the difference in the squalene synthase activity. If the enzyme activity is weaker in ATCC 200589, the activation of the pathways will result in the accumulation of (E,E)-farnesyl diphosphate, the substrate of the enzyme, and following production of (E,E)-farnesol through hydrolysis of (E,E)-farnesyl diphosphate. Recombinant AURGG101 derived from ATCC 200589 produces large amounts of prenyl alcohols. In particular, (E,E)-farnesol in AURGG101 reaches 35.6 mg/l, which is approximately 4fold higher than that in ATCC 200589. HMG1 expression in strain ATCC 200589 increases the production of squalene, (E)-nerolidol, (E,E)-farnesol, and (E,E,E)-geranylgeraniol, whereas that in ATCC 76625 causes high squalene production, low production of (E,E)-farnesol and (E,E,E)-geranylgeraniol, and no (E)-nerolidol production
-
-
-
additional information
?
-
-
method development for rapid and versatile reverse phase -HPLC monitoring for assaying HMGR activity capable of monitoring the levels of both substrates HMG-CoA and NADPH, and products CoA, mevalonate, and NADP+, method evaluation, overview
-
-
-
additional information
?
-
Mus musculus C57BL/6J
-
biphasic regulation of HMG-CoA reductase expression and activity during wound healing and its functional role in the control of keratinocyte angiogenic and proliferative responses, overview
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
(R)-mevalonate + 2 NADP+ + CoA
show the reaction diagram
-
HMGR is a key enzyme in the mevalonate pathway of isoprenoid biosynthesis, the sole route in haloarchaea for lipid and carotenoid production
-
-
?
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
(R)-mevalonate + CoA + 2 NADP+
show the reaction diagram
-
-
-
-
?
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
(R)-mevalonate + CoA + 2 NADP+
show the reaction diagram
-
-
-
-
?
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
(R)-mevalonate + CoA + 2 NADP+
show the reaction diagram
-
-
-
-
?
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
(R)-mevalonate + CoA + 2 NADP+
show the reaction diagram
Q1W675, -
-
-
-
?
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
(R)-mevalonate + CoA + 2 NADP+
show the reaction diagram
Lactococcus lactis NZ9000
-
-
-
-
?
(S)-3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
r
(S)-3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
r
(S)-3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
r
(S)-3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
(S)-3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
r
(S)-3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
enzyme is essential for sterol biosynthesis
-
-
r
(S)-3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
involved in isopentenyl diphosphate biosynthesis, mevalonate pathway overview
-
-
r
(S)-3-hydroxy-3-methylglutaryl-CoA + NADPH
mevaldyl-CoA + NADP+
show the reaction diagram
-
first step reaction
-
-
?
3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
mevalonolactone + CoA + 2 NADP+ + H2O
show the reaction diagram
-
rate-limiting step of cholesterol biosynthesis
-
-
r
3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
mevalonate + CoA + 2 NADP+
show the reaction diagram
-
-
-
-
r
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
r
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
-
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
-
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
ir
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
r
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
-
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
r
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
mevalonate + CoA + NADP+
show the reaction diagram
-
up- and down-regulation of HMGR activity in response to changes in the flux of the mevalonate pathway occur via post-translational control
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
Rattus norvegicus Wistar
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADPH
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
-
-
-
?
acetyl-CoA
acetoacetyl-CoA + CoA
show the reaction diagram
-
-
-
-
r
D-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
(R)-mevalonate + CoA + 2 NADP+
show the reaction diagram
-
-
-
-
r
D-3-hydroxy-3-methylglutaryl-CoA + NADPH
mevalonate + CoA + NADP+
show the reaction diagram
Saccharomyces cerevisiae, Eurotium amstelodami, Aureobasidium pullulans, Debaryomyces hansenii, Hortaea werneckii, Phaeotheca triangularis, Trimmatostroma salinum, Wallemia ichthyophaga, Saccharomyces cerevisiae MZKI K86, Wallemia ichthyophaga EXF 994, Aureobasidium pullulans MZKI B802, Hortaea werneckii MZKI B736, Eurotium amstelodami MZKI A561, Phaeotheca triangularis MZKI B741, Debaryomyces hansenii CBS 767, Trimmatostroma salinum MZKI B734
-
-
-
-
?
hydroxymethylglutaryl-CoA + NADPH + H+
mevalonate + NADP+ + CoA
show the reaction diagram
-
-
-
-
?
hydroxymethylglutaryl-CoA + NADPH + H+
mevalonate + NADP+ + CoA
show the reaction diagram
-
-
-
-
?
hydroxymethylglutaryl-CoA + NADPH + H+
mevalonate + NADP+ + CoA
show the reaction diagram
B2KX91, -
-
-
-
?
hydroxymethylglutaryl-CoA + NADPH + H+
mevalonate + NADP+ + CoA
show the reaction diagram
-
HMGR is the key regulatory enzyme of the mevalonate pathway and also the iridoid biosynthesis, it is highly regulated itself, HMGR may represent a regulator in maintenance of homeostasis between de novo produced and sequestered intermediates of iridoid metabolism, overview
-
-
?
hydroxymethylglutaryl-CoA + NADPH + H+
mevalonate + NADP+ + CoA
show the reaction diagram
-
key enzyme of the mevalonic acid pathway catalysing the first committed step with NADPH as cofactor, overview
-
-
?
hydroxymethylglutaryl-CoA + NADPH + H+
mevalonate + NADP+ + CoA
show the reaction diagram
Mus musculus C57BL/6J
-
-
-
-
?
mevaldyl-CoA + NADPH + H+ + H2O
(R)-mevalonate + CoA + NADP+
show the reaction diagram
-
second step reaction
-
-
?
additional information
?
-
-
enzyme plays a central role in sterol biosynthesis, investigation of the physiological regulation, 3-hydroxy-3-methylglutaryl CoA reductase and C24-sterol methyltransferase type 1 work in concert to control carbon flux into end-product sterols
-
-
-
additional information
?
-
-
enzyme undergoes endoplasmic reticulum-associated degradation which is physiologically regulated by sterol pathway signals, determination of structural features leading to modification and degradation by the quality control system of the endoplasmic reticulum, overview
-
-
-
additional information
?
-
-
phytosterol biosynthetic pathway, overview
-
-
-
additional information
?
-
-
the reaction is a highly regulated process within the cholesterol biosynthetic pathway
-
-
-
additional information
?
-
-
HMG-CoA reductase is regulated by salinity at the level of transcription
-
-
-
additional information
?
-
-
small heterodimer partner nuclear receptor directly regulates cholesterol biosynthesis through inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase
-
-
-
additional information
?
-
-
biphasic regulation of HMG-CoA reductase expression and activity during wound healing and its functional role in the control of keratinocyte angiogenic and proliferative responses, overview
-
-
-
additional information
?
-
-
HMGR activity is not only diminished in iridoid producers but most likely prevalent within the Chrysomelina subtribe and also within the insecta
-
-
-
additional information
?
-
-
the expression of HMGR is regulated in response to non-optimal salinity in the halophilic archaeon
-
-
-
additional information
?
-
-
ubiquitination and proteasomal degradation of microsomal, but not mitochondrial, HMGR isozymes depends on environmental salinity, overview
-
-
-
additional information
?
-
A0N0D3, -
HMGR can accelerate the biosynthesis of carotenoids in the Escherichia coli transformant, it plays an influential role in isoprenoid biosynthesis
-
-
-
additional information
?
-
Mus musculus C57BL/6J
-
biphasic regulation of HMG-CoA reductase expression and activity during wound healing and its functional role in the control of keratinocyte angiogenic and proliferative responses, overview
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
NADPH
B2KX91
dependent on
NADPH
Q1W675
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Hg2+
-
induces the enzyme in cut roots treated with HgCl2
NaCl
-
specific HMGR activity is responsive to changes in NaCl concentrations. Minimal activity under optimal conditions and an increase in HMGR activities and protein levels under hyposaline and hypersaline conditions. HMGR activity is crucial for halotolerance as well as for the changes in protein prenylation in response to changing salinity
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(3R,5R)-7-(1-ethyl-3-(4-fluorophenyl)-4-methyl-5-[(5-methyl-pyrazin-2-ylmethyl)-carbamoyl]-1H-pyrrol-2-yl)-3,5-dihydroxy-heptanoic acid sodium salt
-
-
(3R,5R)-7-[1-ethyl-3-(4-fluorophenyl)-4-methyl-5-phenylcarbamoyl-1H-pyrrol-2-yl]-3,5-dihydroxy-heptanoicacid sodium salt
-
-
-
(3R,5R)-7-[1-ethyl-3-(4-fluorophenyl)-5-(4-methoxybenzylcarbamoyl)-4-methyl-1H-pyrrol-2-yl]-3,5-dihydroxy-heptanoic acid sodium salt
-
-
(3R,5R)-7-[1-ethyl-3-(4-fluorophenyl)-5-(4-methoxycarbonyl-benzylcarbamoyl)-4-methyl-1H-pyrrol-2-yl]-3,5-dihydroxy-heptanoic acid sodium salt
-
-
-
(3R,5R)-7-[3-(4-fluoro-phenyl)-1-isopropyl-5-phenylcarbamoyl-4-pyridin-2-yl-1H-pyrrol-2-yl]-3,5-dihydroxy-heptanoic acid sodium salt
-
-
-
(3R,5R)-7-[3-(4-fluorophenyl)-1-isopropyl-4-phenyl-5-phenylcarbamoyl-1H-pyrrol-2-yl]-3,5-dihydroxy-heptanoic acid sodium salt
-
-
-
(3R,5R)-7-[3-(4-fluorophenyl)-5-[(3-methoxybenzyl)carbamoyl]-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
-
(3R,5R)-7-[3-(4-fluorophenyl)-5-[[4-(methoxymethyl)benzyl]carbamoyl]-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
-
(3R,5R)-7-[5-(4-carboxy-benzylcarbamoyl)-ethyl-3-(4-fluorophenyl)-4-methyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoicacid disodium salt
-
-
(3R,5R)-7-[5-benzylcarbamoyl-3-(4-fluoro-phenyl)-1-isopropyl-4-pyridin-2-yl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoicacid
-
-
(3R,5R)-7-[5-carbamoyl-1-ethyl-3-(4-fluorophenyl)-4-methyl-1H-pyrrol-2-yl]-3,5-dihydroxy-heptanoic acid sodium salt
-
-
-
(3R,5R)-7-[5-carbamoyl-3-(4-fluoro-phenyl)-1-isopropyl-4-pyridin-2-yl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoicacid sodium salt
-
-
-
(3R,5R)-7-[5-cyano-3-(4-fluoro-phenyl)-1-isopropyl-4-pyridin-2-yl-1H-pyrrol-2-yl]-3,5-dihydroxy-heptanoicacid sodium salt
-
-
-
(3R,5R)-7-[5-[(3-carbamoylbenzyl)carbamoyl]-3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
-
(3R,5R)-7-[5-[(4-cyanobenzyl)carbamoyl]-3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
-
(3R,5R)-7-[5-[[4-(dimethylcarbamoyl)benzyl]carbamoyl]-3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
-
(5S)-5-hydroxy-4-{2-[(1S,2R,4aR)-1,2,4a,5-tetramethyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl]ethyl}furan-2(5H)-one
-
22.65% inhibition of HMG-CoA reductase at 0.001 mM concentration and maximum inhibition of 78.03% at 0.1 mM, the HMG-CoA reductase inhibitor, a clerodane diterpene from ethanolic extract of Polyalthia longifolia var. pendula, is a potential lipid lowering agent, molecular docking analysis, overview
(E,3R,5S)-7-(4-(3-(4-fluorophenyl)pentan-3-yl)-2-isopropylphenyl)-3,5-dihydroxyhept-6-enoic acid
-
competitive inhibitor, shows slight inhibitory activity
(R)-3-hydroxy-3-methylglutaryl-CoA
-
competitive inhibitor
(S)-4-carboxy-3-hydroxy-3-methylbutyryl-CoA
-
competitive inhibitor
(S)-4-carboxy-3-hydroxybutyryl-CoA
-
competitive inhibitor
1,10-phenanthroline
-
-
3,3-dimethylglutaryl-CoA
-
competitive inhibitor
3-hydroxy-3-methylglutaryl-CoA
-
0.05 mM
3-Hydroxyglutaryl-CoA
-
competitive inhibitor
3-methylglutaryl-CoA
-
competitive inhibitor
4-[[([5-[(3R,5R)-6-carboxy-3,5-dihydroxyhexyl]-4-(4-fluorophenyl)-1-(1-methylethyl)-3-phenyl-1H-pyrrol-2-yl]carbonyl)amino]methyl]benzoic acid
-
-
7-[3,4-bis(4-fluorophenyl)-1-(1-methylethyl)-5-(phenylcarbamoyl)-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
-
7-[3,4-bis(4-fluorophenyl)-5-[(3-hydroxyphenyl)carbamoyl]-1-(1-methylethyl)-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
-
7-[3,4-bis(4-fluorophenyl)-5-[(3-methoxyphenyl)carbamoyl]-1-(1-methylethyl)-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
-
7-[3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-5-(phenylcarbamoyl)-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
-
7-[3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-5-(propylcarbamoyl)-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
-
7-[3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-5-[(4-sulfamoylphenyl)carbamoyl]-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
-
7-[3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-5-[(pyridin-2-ylmethyl)carbamoyl]-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
-
7-[3-(4-fluorophenyl)-1-(1-methylethyl)-5-[[(4-methyl-1,3-thiazol-2-yl)methyl]carbamoyl]-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
-
7-[3-(4-fluorophenyl)-1-(1-methylethyl)-5-[[(5-methyl-1H-imidazol-2-yl)methyl]carbamoyl]-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
-
7-[3-(4-fluorophenyl)-1-(1-methylethyl)-5-[[(5-methyl-1H-pyrazol-3-yl)methyl]carbamoyl]-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
-
7-[3-(4-fluorophenyl)-5-(methylcarbamoyl)-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
-
7-[3-(4-fluorophenyl)-5-[(4-hydroxyphenyl)carbamoyl]-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
-
7-[3-(4-fluorophenyl)-5-[(4-methoxybenzyl)carbamoyl]-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
-
7-[5-(benzylcarbamoyl)-3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
-
7-[5-(cyclopropylcarbamoyl)-3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
-
7-[5-(dimethylcarbamoyl)-3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
-
7-[5-(ethylcarbamoyl)-3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
-
7-[5-carbamoyl-3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
-
7-[5-ethylcarbamoyl-3-(4-fluoro-phenyl)-1-isopropyl-4-pyridin-2-yl-1H-pyrrol-2-yl]-3,5-dihydroxy-heptanoicacid sodium salt
-
-
-
7-[5-[(4-carbamoylphenyl)carbamoyl]-3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
-
7-[5-[(4-carboxyphenyl)carbamoyl]-3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
-
7-[5-[[(1,5-dimethyl-1H-pyrazol-3-yl)methyl]carbamoyl]-3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
-
7-[5-[[3-(dimethylcarbamoyl)phenyl]carbamoyl]-3,4-bis(4-fluorophenyl)-1-(1-methylethyl)-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
-
7-[5-[[4-(dimethylcarbamoyl)phenyl]carbamoyl]-3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
-
8-hydroxygeraniol
-
competitive inhibition mechanism, binds at the catalytic site, docking experiments, overview
acetoacetyl-CoA
-
-
adenosine-2'-monophospho-5'-diphosphoribose
-
competitive inhibitor for NADPH binding site
AFGYVAE peptide
-
-
-
atorvastatin
-
-
atorvastatin
-
-
atorvastatin
-
-
atorvastatin
-
has a differentiating effect on wild-type and mutant forms of the human protein
brutieridin
-
i.e. hesperetin 7-(2''-alpha-rhamnosyl-6''-(3''''-hydroxy-3''''-methylglutaryl)-beta-D-glucoside), a flavonoid conjugate from bergamot fruit extract, structural analogue of statins, computational study, overview
ceramide
-
treatment with exogenous ceramides, or increasing the endogenous ceramide levels inhibits HMGCR by 6080%
cerivastatin
-
biphasic inhibition mechanism, slow, tight-binding type of inhibitor
cerivastatin
-
-
cerivastatin
-
-
CoA disulfide
-
no inactivation in presence of NADPH 1 mM, or HMG-CoA 0.5 mM
Compactin
-
competitive inhibitor for HMG-CoA binding site
cycloheximide
-
downregulation of protein synthesis, synergistic with eicosapentanoic acid and myristic acid
daidzein
-
isoflavone, isolated and purified from korean soybean paste, structural analysis
deoxycholate
-
-
DFGYVAE peptide
-
-
-
digitonine
-
2% digitonin, 80% inhibition
EFGYVAE peptide
-
-
-
eicosapentaenoic acid
-
inhibits translation of the enzyme about 50% at 0.15 mM, downregulation, slightly increases downregulation of protein synthesis by cycloheximide
F(4-fluoro)VAE
-
HMG-CoA competitive inhibitor
FFGYVAE peptide
-
-
-
FFYVAE peptide
-
-
-
FG-(4-fluoro)FVAE peptide
-
-
-
FGYVAE peptide
-
-
-
fluvastatin
-
competitive inhibitor
fluvastatin
-
competitive
fluvastatin
-
has a differentiating effect on wild-type and mutant forms of the human protein
FPYVAE peptide
-
-
-
FVAE
-
HMG-CoA competitive inhibitor
genistein
-
isoflavone, isolated and purified from korean soybean paste, structural analysis
GFGYVAE peptide
-
-
-
GFPDGG
-
designed on the basis of the rigid peptide backbone, increases the inhibitory potency more than 300 times compared to the first isolated LPYP from soybean, overview
GFPEGG
-
HMG-CoA competitive inhibitor
GFPTGG
-
HMG-CoA competitive inhibitor; NADPH and HMG-CoA competitive inhibitor
GFPTGG
-
competitive, effects on enzyme Michaelis-Menten kinetics, overview
GLPDGG
-
NADPH and HMG-CoA competitive inhibitor
GLPEGG
-
NADPH and HMG-CoA competitive inhibitor
GLPTGG
-
NADPH and HMG-CoA competitive inhibitor
GLPTGG
-
competitive
glycitein
-
isoflavone, isolated and purified from korean soybean paste, structural analysis
Hydroxymethylglutarate
-
2 mM, slightly inhibitory
Hydroxymethylglutarate
-
-
IAVE
-
HMG-CoA competitive inhibitor
IAVE peptide
-
-
-
IAVP
-
NADPH competitive inhibitor
IAVPGEVA
-
isolated from soybean by pepsin
IAVPGEVA peptide
-
-
-
IAVPTGVA peptide
-
-
-
IFGYVAE peptide
-
-
-
IVAE
-
HMG-CoA competitive inhibitor
IVAE peptide
-
-
-
LFGYVAE peptide
-
-
-
lovastatin
-
competitive inhibitor for HMG-CoA binding site
lovastatin
-
competitive inhibitor for HMG-CoA binding site and noncompetitive inhibitor for NADPH binding site
lovastatin
-
competitive inhibitor for HMG-CoA binding site
lovastatin
-, Q7YT62, Q7YT63
-
lovastatin
-
slightly inhibitory statin for class II enzyme, binding structure at the active site involves the residues Lys267, Asn271, Glu83, Arg261, and 2 water molecules, substrate mimicking binding mode
lovastatin
-
no effect of lovastatin on the growth curve of Hortaea werneckii in salt-free media, whereas remarkably reduced growth in the otherwise physiologically optimal medium containing 17% NaCl, an effect even more pronounced in hypersaline medium containing 25% NaCl. Inhibition of HMGR in vivo by lovastatin impairs the halotolerant character
lovastatin
-
-
lovastatin
-
the representative of the statin class of drugs that in their active hydrolysed form are specific inhibitors of the enzyme
LPYP
-
from soybean
LPYP peptide
-
-
-
melitidin
-
i.e. naringenin 7-(2''-alpha-rhamnosyl-6''-(3''''-hydroxy-3''''-methylglutaryl)-beta-D-glucoside), a flavonoid conjugate from bergamot fruit extract, structural analogue of statins, computational study, overview
mevalonic acid
-, Q7YT62, Q7YT63
-
mevastatin
-
-
Mevinolin
-
competitive with 3-hydroxy-3-methylglutaryl-CoA
myriocin
-
concomitant reduction of both HMGR activity and the sterol content by depletion of the sphingolipid pathway. At 0.01 mM myriocin decrease to ca. 55% of the HMGR activity in control plants. Myriocin-induced down-regulation of HMGR activity is exerted at the post-translational level, like the regulatory response of HMGR to enhancement or depletion of the flux through the sterol pathway
p-chloromercuribenzoate
-
1 mM, complete inhibition
p-hydroxymercuribenzoate
-
3.7 mM, complete inhibition
p-hydroxymercuribenzoate
-
0.01 mM inhibited 97% of reduction
PFGYVAE peptide
-
-
-
pravastatin
-
inhibitory in the presence of increasing concentrations of NADPH, but increasing concentrations of HMG-CoA block the HMG-CoA reductase-inhibiting activity
rosuvastatin
-
thermodynamics of binding and inhibition mechanism, Glu559 is involved, reversible, 2-step complex formation, competitive with respect to 3-hydroxy-3-methylglutaryl-CoA, non-competitive to NADPH
rosuvastatin
-
-
rosuvastatin
-
-
rosuvastatin
-
-
SFGYVAE peptide
-
most active inhibitory peptide; shows high ability to inhibit HMGR by competitive inhibition with respect to (S)-3-hydroxy-3-methylglutaryl-CoA
-
simvastatin
-
-
simvastatin
-
enzyme inhibition causes 40% reduction of wound healing, inhibition of HMGR activity during acute wound healing interferes with keratinocyte VEGF production and proliferation at the wound site, overview
simvastatin
-
does not allow differentiation between the wild-type and mutant forms of the human protein
small heterodimer partner nuclear receptor
-
directly regulates cholesterol biosynthesis through inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase
-
SMase C
-
treatment of fibroblasts with SMase C results in a 90% inhibition of HMGCR
-
SMase D
-
treatment of fibroblasts with SMase D inhibits by 29%
-
sodium (E,3R,5S)-7-(2-(2-fluorophenyl)-4-(3-phenylpentan-3-yl)phenyl)-3,5-dihydroxy-hept-6-enoate
-
has almost no effect on the activity
sodium (E,3R,5S)-7-(2-(3-fluorophenyl)-4-(3-phenylpentan-3-yl)phenyl)-3,5-dihydroxy-hept-6-enoate
-
-
sodium (E,3R,5S)-7-(2-(4-fluorophenyl)-4-(3-phenylpentan-3-yl)phenyl)-3,5-dihydroxy-hept-6-enoate
-
shows the most potent inhibitory activity among compounds comparable with that of clinically useful mevastatin
sodium (E,3R,5S)-7-(2-phenyl-4-(3-phenylpentan-3-yl)phenyl)-3,5-dihydroxyhept-6-enoate
-
has almost no effect on the activity
sodium (E,3R,5S)-7-(4-(3-(2-fluorophenyl)pentan-3-yl)-2-isopropylphenyl)-3,5-dihydroxyhept-6-enoate
-
-
sodium (E,3R,5S)-7-(4-(3-(3-fluorophenyl)pentan-3-yl)-2-isopropylphenyl)-3,5-dihydroxyhept-6-enoate
-
-
sodium (E,3R,5S)-7-(4-(3-phenylpentan-3-yl)-2-isopropylphenyl)-3,5-dihydroxyhept-6-enoate
-
-
squalestatin
-
mutant plants, not wild-type plants, become sterile
TFGYVAE peptide
-
-
-
VFGYVAE peptide
-
-
-
YAVE
-
HMG-CoA competitive inhibitor
YAVE peptide
-
-
-
YVAE
-
HMG-CoA competitive inhibitor
YVAE peptide
-
-
-
additional information
-, Q7YT62, Q7YT63
no inhibition by farnesoate and farnesoic acid
-
additional information
-
the hybrid is resistant to race 0 of Phytophtora infestans
-
additional information
-
27-hydroxycholesterol strongly supresses the expression of HMGR, the in vivo inhibition of sterol 27-hydroxylase CYP27A1, e.g. by the drugs rapamycin and cyclosporine A, reduces the inhibition and thus increases HMGR activity, overview
-
additional information
-
discovery, synthesis, and optimization of substituted pyrrole-based hepatoselective ligands as potent inhibitors of HMG-CoA reductase for reducing low density lipoprotein cholesterol (LDL-c) in the treatment of hypercholesterolemia
-
additional information
-
inhibition potency of inhibitors in hepatocytes, myocytes and on purified enzye, overview
-
additional information
-
the activity of microsomal isoyzme Hmg2 is highest under hypo-saline and extremely hyper-saline conditions, and down-regulated under optimal growth conditions
-
additional information
-
no inhibition by geraniol or by its glucoside and thioglucoside
-
additional information
-
design, synthesis and evaluation of structure-based peptide inhibitors, computational methods, overview
-
additional information
-
(E,3R,5S)-7-(4-(3-(4-fluorophenyl)pentan-3-yl)phenyl)-3,5-dihydroxyhept-6-enoic acid shows no apparent HMGR inhibitory activity even at 100 mM
-
additional information
-
whether plants are grown with mevalonate from the beginning or only during the last 9 days, HMGR activity is drastically reduced to 25% of the activity in plants grown in the absence of mevalonate. Plants grown without mevalonate during the last 9 days show a severe, though less pronounced, reduction in HMGR activity, which decreases to 60% of the activity in control plants. Significant reduction of HMGR activity does not correlate with changes in both the expression of HMG1 and HMG2 genes and the amount of HMGR protein
-
additional information
-
screening of eight-membered medium ring lactams and related tricyclic compounds, either seven-membered lactams, thiolactams or amines, for inhibitory potency, overview. The compounds are inhibitory also in the presence of increasing concentrations of NADPH, and are not affected by increasing concentrations of HMG-CoA. Medium ring lactams and existing statins may have different mechanisms of enzyme interaction and inhibition, molecular docking studies and comparisons using the HMG-CoA reductase statin-binding receptor model, overview. The ligands may occupy a narrow channel housing the pyridinium moiety on NADP+
-
additional information
-
methanolic extracts of Quercus infectoria galls, Rosa damascena flowers, and Myrtus communis leaves inhibit the enzyme activity noncompetitively to 84%, 70%, and 62%, respectively. Extracts of diverse other plants are also inhibitory for the enzyme, detailed overview
-
additional information
-
statins are potent enzyme inhibitors that bind to the active site where also the natural substrate binds, used widely in the treatment of hypercholesterolemia
-
additional information
-
design of highly potent and competitive inhibitory peptides for 3-hydroxy-3-methylglutaryl CoA reductase, no inhibition with SFGYVAG peptide
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
myristic acid
-
stimulates translation of the enzyme about 1.8fold at 0.15 mM, upregulation
squalestatin
-
leads to a significant concentration-dependent activation of HMGR of ca. 3fold the activity in untreated plants. Maximal HMGR activation at 0.06 mM squalestatin. No relevant changes in the level of expression of the HMG genes or in the amount of HMGR protein
supernatant protein factor
-
i.e. SPF, a 46 kDa cytosolic protein, stimulation of squalene monooxygenase and cholesterol biosynthesis in hepatoma cell culture, acts directly on the enzyme, not by increasing the enzyme amount
-
terbinafine
-
leads to a significant concentration-dependent activation of HMGR of ca. 3fold the activity in untreated plants. Maximal HMGR activation at 0.75 mM terbinafine. No relevant changes in the level of expression of the HMG genes or in the amount of HMGR protein
dithiothreitol
-
2 mM
additional information
-
4fold enzyme induction by root cutting within 2 h, and strong induction by infection with Phytophtora infestans, maximal 66fold after 2 h, induction mechanism
-
additional information
-
about 40fold enzyme induction by root cutting within 14 h, and about 875fold induction by infection with Phytophtora infestans after 22 h, induction mechanism
-
additional information
-
the activity of microsomal isoyzme Hmg2 is highest under hypo-saline and extremely hyper-saline conditions, and down-regulated under optimal growth conditions
-
additional information
-
phosphorylation of HMGCR is stimulated by SMase C or exogenous ceramide
-
additional information
-
leaf tissue of Artemisia annua transgenic lines possess significantly higher HMGR activity compared with wild-type controls, and this activity is associated exclusively with microsomal membranes and with higher artemisinin content (increase of up to 22.5% artemisin in content compared with wild-type control Artemisia annua plants)
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.252
-
(R)-mevalonate
-
pH 8.3, 25C
1
-
(R)-mevalonate
-
pH 6.5, 37C, oxidation
0.04
-
(R,S)-3-hydroxy-3-methylglutaryl-CoA
-
-
0.056
-
(R,S)-3-hydroxy-3-methylglutaryl-CoA
-
-
0.47
-
(R,S)-mevaldehyde
-
oxidative acylation of (R,S)-mevaldehyde
0.55
-
(R,S)-mevaldehyde
-
reduction of (R,S)-mevaldehyde
0.013
-
(S)-3-hydroxy-3-methylglutaryl-CoA
-
pH 6.8, 25C
0.02
-
(S)-3-hydroxy-3-methylglutaryl-CoA
-
pH 6.5, 37C
0.06
-
(S)-3-hydroxy-3-methylglutaryl-CoA
-
-
0.003
-
3-hydroxy-3-methylglutaryl-CoA
-
-
0.006
-
3-hydroxy-3-methylglutaryl-CoA
-
only one enantiomer
0.008
-
3-hydroxy-3-methylglutaryl-CoA
-
-
0.01
-
3-hydroxy-3-methylglutaryl-CoA
-
reductase from tumor
0.012
-
3-hydroxy-3-methylglutaryl-CoA
-
-
0.014
-
3-hydroxy-3-methylglutaryl-CoA
-
reductase from liver and reductase from tumor
0.015
-
3-hydroxy-3-methylglutaryl-CoA
-
reductase from liver, implanted tumor
0.017
-
3-hydroxy-3-methylglutaryl-CoA
-
; pH 5.5, 50C
0.019
-
3-hydroxy-3-methylglutaryl-CoA
-
reductase from liver, implanted tumor
0.021
-
3-hydroxy-3-methylglutaryl-CoA
-
-
0.024
-
3-hydroxy-3-methylglutaryl-CoA
-
reductase from liver
0.028
-
3-hydroxy-3-methylglutaryl-CoA
-
-
0.045
-
3-hydroxy-3-methylglutaryl-CoA
-
wild type
0.07
-
3-hydroxy-3-methylglutaryl-CoA
-
-
0.076
-
3-hydroxy-3-methylglutaryl-CoA
-
mutant
0.6
-
3-hydroxy-3-methylglutaryl-CoA
-
pH 7.5, temperature not specified in the publication
0.074
-
CoA
-
pH 8.3, 25C
0.22
-
CoA
-
pH 6.5, 37C, mevaldehyde oxidation
0.23
-
CoA
-
pH 6.5, 37C, mevalonate oxidation
0.00011
-
CoASH
-
pH 9.0, 50C, wild-type
0.00015
-
CoASH
-
pH 9.0, 50C, mutant L403R/G404R/A406S
0.045
-
HMG-CoA
-
pH 5.5, 50C, wild-type
0.076
-
HMG-CoA
-
pH 5.5, 50C, mutant L403R/G404R/A406S
0.068
-
hydroxymethylglutaryl-CoA
-
-
0.0043
-
mevaldehyde
-
pH 5.0, 50C, wild-type
0.0063
-
mevaldehyde
-
pH 5.0, 50C, mutant L403R/G404R/A406S
0.66
-
mevaldehyde
-
pH 6.5, 37C, oxidation
3.8
-
mevaldehyde
-
pH 6.5, 37C, reduction
0.0015
-
mevalonate
-
pH 9.0, 50C, wild-type
0.0009
-
NADP+
-
pH 9.0, 50C, wild-type
0.0013
-
NADP+
-
pH 9.0, 50C, mutant L403R/G404R/A406S
0.035
-
NADP+
-
-
0.22
-
NADP+
-
pH 8.3, 25C
0.25
-
NADP+
-
pH 6.5, 37C, mevalonate oxidation
0.67
-
NADP+
-
pH 6.5, 37C, mevaldehyde oxidation
0.021
-
NADPH
-
-
0.023
-
NADPH
-
; pH 5.5, 50C
0.03
-
NADPH
-
pH 6.5, 37C, (S)-3-hydroxy-3-methylglutaryl-CoA reduction
0.032
-
NADPH
-
reduction of R,S-mevaldehyde
0.037
-
NADPH
-
-
0.043
-
NADPH
-
pH 6.8, 25C
0.052
-
NADPH
-
-
0.055
-
NADPH
-
pH 5.5, 50C, wild-type; wild type
0.062
-
NADPH
-
-
0.066
-
NADPH
-
-
0.081
-
NADPH
-
-
0.083
-
NADPH
-
mutant; pH 5.5, 50C, mutant L403R/G404R/A406S
0.25
-
NADPH
-
pH 6.5, 37C, mevaldehyde reduction
0.004
-
S-3-hydroxy-3-methylglutaryl-CoA
-
-
0.0017
-
mevalonate
-
pH 9.0, 50C, mutnant L403R/G404R/A406S
additional information
-
additional information
-
kinetic analysis
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.023
-
hydroxymethylglutaryl-CoA
-
-
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
8e-06
-
atorvastatin
-
-
1.4e-05
-
atorvastatin
-
pH 6.8, 37C
5.7e-06
-
cerivastatin
-
pH 6.8, 37C
1e-05
-
cerivastatin
-
-
2.8e-05
-
fluvastatin
-
-
0.000256
-
fluvastatin
-
pH 6.8, 37C
0.027
-
fluvastatin
-
pH 6.8, 25C, versus (S)-3-hydroxy-3-methylglutaryl-CoA
0.0064
-
GFPTGG
-
-
4.5e-07
-
lovastatin
-, Q7YT62, Q7YT63
pH 7.4, recombinant isozyme HMGR1
0.081
-
mevalonic acid
-, Q7YT62, Q7YT63
pH 7.4, recombinant isozyme HMGR1
4.4e-05
-
pravastatin
-
-
0.000103
-
pravastatin
-
pH 6.8, 37C
2.3e-06
-
rosuvastatin
-
pH 6.8, 37C
3.5e-06
-
rosuvastatin
-
-
1.2e-05
-
SFGYVAE peptide
-
pH and temperature not specified in the publication
-
1.1e-05
-
simvastatin
-
-
5e-06
-
Mevinolin
-
pH 5.5, 50C
additional information
-
additional information
-
steady state inhibition kinetics
-
additional information
-
additional information
-
inhibition kinetics of different plant extracts, overview
-
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
3.5e-07
-
(3R,5R)-7-(1-ethyl-3-(4-fluorophenyl)-4-methyl-5-[(5-methyl-pyrazin-2-ylmethyl)-carbamoyl]-1H-pyrrol-2-yl)-3,5-dihydroxy-heptanoic acid sodium salt
-
37C, hepatocytes
2.9e-07
-
(3R,5R)-7-[1-ethyl-3-(4-fluorophenyl)-4-methyl-5-phenylcarbamoyl-1H-pyrrol-2-yl]-3,5-dihydroxy-heptanoicacid sodium salt
-
37C, hepatocytes
-
2.4e-07
-
(3R,5R)-7-[1-ethyl-3-(4-fluorophenyl)-5-(4-methoxybenzylcarbamoyl)-4-methyl-1H-pyrrol-2-yl]-3,5-dihydroxy-heptanoic acid sodium salt
-
37C, hepatocytes
2.8e-07
-
(3R,5R)-7-[1-ethyl-3-(4-fluorophenyl)-5-(4-methoxycarbonyl-benzylcarbamoyl)-4-methyl-1H-pyrrol-2-yl]-3,5-dihydroxy-heptanoic acid sodium salt
-
37C, hepatocytes
-
1.7e-07
-
(3R,5R)-7-[3-(4-fluoro-phenyl)-1-isopropyl-5-phenylcarbamoyl-4-pyridin-2-yl-1H-pyrrol-2-yl]-3,5-dihydroxy-heptanoic acid sodium salt
-
37C, hepatocytes
-
4.3e-07
-
(3R,5R)-7-[3-(4-fluorophenyl)-1-isopropyl-4-phenyl-5-phenylcarbamoyl-1H-pyrrol-2-yl]-3,5-dihydroxy-heptanoic acid sodium salt
-
37C, hepatocytes
-
1.8e-06
-
(3R,5R)-7-[3-(4-fluorophenyl)-5-[(3-methoxybenzyl)carbamoyl]-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
inhibition of purified enzyme
7e-07
-
(3R,5R)-7-[3-(4-fluorophenyl)-5-[[4-(methoxymethyl)benzyl]carbamoyl]-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
inhibition of purified enzyme
1.1e-07
-
(3R,5R)-7-[5-(4-carboxy-benzylcarbamoyl)-ethyl-3-(4-fluorophenyl)-4-methyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoicacid disodium salt
-
37C, hepatocytes
1.5e-07
-
(3R,5R)-7-[5-benzylcarbamoyl-3-(4-fluoro-phenyl)-1-isopropyl-4-pyridin-2-yl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoicacid
-
37C, hepatocytes
3.2e-05
-
(3R,5R)-7-[5-carbamoyl-1-ethyl-3-(4-fluorophenyl)-4-methyl-1H-pyrrol-2-yl]-3,5-dihydroxy-heptanoic acid sodium salt
-
37C, hepatocytes
-
4.9e-06
-
(3R,5R)-7-[5-carbamoyl-3-(4-fluoro-phenyl)-1-isopropyl-4-pyridin-2-yl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoicacid sodium salt
-
37C, hepatocytes
-
2.1e-06
-
(3R,5R)-7-[5-cyano-3-(4-fluoro-phenyl)-1-isopropyl-4-pyridin-2-yl-1H-pyrrol-2-yl]-3,5-dihydroxy-heptanoicacid sodium salt
-
37C, hepatocytes
-
1.2e-06
-
(3R,5R)-7-[5-[(3-carbamoylbenzyl)carbamoyl]-3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
inhibition of purified enzyme
2e-07
-
(3R,5R)-7-[5-[(4-cyanobenzyl)carbamoyl]-3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
inhibition of purified enzyme
1.2e-06
-
(3R,5R)-7-[5-[[4-(dimethylcarbamoyl)benzyl]carbamoyl]-3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
inhibition of purified enzyme
2.2
-
(E,3R,5S)-7-(4-(3-(4-fluorophenyl)pentan-3-yl)-2-isopropylphenyl)-3,5-dihydroxyhept-6-enoic acid
-
DL-[3-14C]3-hydroxy-3-methylglutaryl-CoA (0.37 MBq) and 10 mg protein of microsomal fraction incubated at 37C for 30 min
26
-
(E,3R,5S)-7-(4-(3-(4-fluorophenyl)pentan-3-yl)-2-isopropylphenyl)-3,5-dihydroxyhept-6-enoic acid
-
DL-[3-14C]3-hydroxy-3-methylglutaryl-CoA (3.7 MBq) and 10 mg protein of microsomal fraction incubated at 37C for 30 min
2.2e-06
-
4-[[([5-[(3R,5R)-6-carboxy-3,5-dihydroxyhexyl]-4-(4-fluorophenyl)-1-(1-methylethyl)-3-phenyl-1H-pyrrol-2-yl]carbonyl)amino]methyl]benzoic acid
-
inhibition of purified enzyme
1.8e-06
-
7-[3,4-bis(4-fluorophenyl)-1-(1-methylethyl)-5-(phenylcarbamoyl)-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
inhibition of purified enzyme
7e-07
-
7-[3,4-bis(4-fluorophenyl)-5-[(3-hydroxyphenyl)carbamoyl]-1-(1-methylethyl)-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
inhibition of purified enzyme
6.6e-06
-
7-[3,4-bis(4-fluorophenyl)-5-[(3-methoxyphenyl)carbamoyl]-1-(1-methylethyl)-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
inhibition of purified enzyme
1.24e-05
-
7-[3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-5-(phenylcarbamoyl)-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
inhibition of purified enzyme
1.5e-05
-
7-[3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-5-(propylcarbamoyl)-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
inhibition of purified enzyme
2.9e-06
-
7-[3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-5-[(4-sulfamoylphenyl)carbamoyl]-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
inhibition of purified enzyme
8e-07
-
7-[3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-5-[(pyridin-2-ylmethyl)carbamoyl]-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
inhibition of purified enzyme
1.5e-06
-
7-[3-(4-fluorophenyl)-1-(1-methylethyl)-5-[[(4-methyl-1,3-thiazol-2-yl)methyl]carbamoyl]-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
inhibition of purified enzyme
3.4e-06
-
7-[3-(4-fluorophenyl)-1-(1-methylethyl)-5-[[(5-methyl-1H-imidazol-2-yl)methyl]carbamoyl]-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
inhibition of purified enzyme
2.6e-06
-
7-[3-(4-fluorophenyl)-1-(1-methylethyl)-5-[[(5-methyl-1H-pyrazol-3-yl)methyl]carbamoyl]-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
inhibition of purified enzyme
8.8e-06
-
7-[3-(4-fluorophenyl)-5-(methylcarbamoyl)-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
inhibition of purified enzyme
4e-07
-
7-[3-(4-fluorophenyl)-5-[(4-hydroxyphenyl)carbamoyl]-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
inhibition of purified enzyme
8e-07
-
7-[3-(4-fluorophenyl)-5-[(4-methoxybenzyl)carbamoyl]-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
inhibition of purified enzyme
8e-07
-
7-[5-(benzylcarbamoyl)-3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
inhibition of purified enzyme
3.8e-06
-
7-[5-(cyclopropylcarbamoyl)-3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
inhibition of purified enzyme
2e-05
-
7-[5-(dimethylcarbamoyl)-3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
inhibition of purified enzyme
1.2e-05
-
7-[5-(ethylcarbamoyl)-3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
inhibition of purified enzyme
3e-06
-
7-[5-carbamoyl-3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
inhibition of purified enzyme
5.1e-06
-
7-[5-ethylcarbamoyl-3-(4-fluoro-phenyl)-1-isopropyl-4-pyridin-2-yl-1H-pyrrol-2-yl]-3,5-dihydroxy-heptanoicacid sodium salt
-
37C, hepatocytes
-
3e-07
-
7-[5-[(4-carbamoylphenyl)carbamoyl]-3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
inhibition of purified enzyme
3e-07
-
7-[5-[(4-carboxyphenyl)carbamoyl]-3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
inhibition of purified enzyme
6e-07
-
7-[5-[[(1,5-dimethyl-1H-pyrazol-3-yl)methyl]carbamoyl]-3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
inhibition of purified enzyme
3e-07
-
7-[5-[[3-(dimethylcarbamoyl)phenyl]carbamoyl]-3,4-bis(4-fluorophenyl)-1-(1-methylethyl)-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
inhibition of purified enzyme
1.4e-06
-
7-[5-[[4-(dimethylcarbamoyl)phenyl]carbamoyl]-3-(4-fluorophenyl)-1-(1-methylethyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoate
-
inhibition of purified enzyme
1.2
-
8-hydroxygeraniol
-
pH 6.8, 30C, recombinant catalytic domain
0.00049
-
AFGYVAE peptide
-
pH and temperature not specified in the publication
-
1.7e-06
-
cerivastatin
-
37C, hepatocytes
0.00016
-
DFGYVAE peptide
-
pH and temperature not specified in the publication
-
0.00024
-
EFGYVAE peptide
-
pH and temperature not specified in the publication
-
0.0038
-
F(4-fluoro)VAE
-
-
0.00032
-
FFGYVAE peptide
-
pH and temperature not specified in the publication
-
0.0025
-
FFYVAE peptide
-
pH and temperature not specified in the publication
-
0.0085
-
FG-(4-fluoro)FVAE peptide
-
pH and temperature not specified in the publication
-
0.0004
-
FGYVAE peptide
-
pH and temperature not specified in the publication
-
0.00022
-
fluvastatin
-
pH 6.8, 30C
0.003
-
fluvastatin
-
DL-[3-14C]3-hydroxy-3-methylglutaryl-CoA (0.37 MBq) and 10 mg protein of microsomal fraction incubated at 37C for 30 min
0.0014
-
FPYVAE peptide
-
pH and temperature not specified in the publication
-
0.0438
-
FVAE
-
-
0.00027
-
GFGYVAE peptide
-
pH and temperature not specified in the publication
-
0.0015
-
GFPDGG
-
-
0.0017
-
GFPEGG
-
-
0.0169
-
GFPTGG
-
-
0.0223
-
GLPDGG
-
-
0.0272
-
GLPEGG
-
-
0.0194
-
GLPTGG
-
-
0.0752
-
IAVE
-
-
0.075
-
IAVE peptide
-
pH and temperature not specified in the publication
-
0.097
-
IAVP
-
-
0.152
-
IAVPGEVA
-
-
0.201
-
IAVPGEVA peptide
-
pH and temperature not specified in the publication
-
0.152
-
IAVPTGVA peptide
-
pH and temperature not specified in the publication
-
0.00035
-
IFGYVAE peptide
-
pH and temperature not specified in the publication
-
0.0441
-
IVAE
-
-
0.052
-
IVAE peptide
-
pH and temperature not specified in the publication
-
0.00037
-
LFGYVAE peptide
-
pH and temperature not specified in the publication
-
0.484
-
LPYP
-
-
0.484
-
LPYP peptide
-
pH and temperature not specified in the publication
-
0.04
-
mevastatin
-
DL-[3-14C]3-hydroxy-3-methylglutaryl-CoA (0.37 MBq) and 10 mg protein of microsomal fraction incubated at 37C for 30 min
0.00043
-
PFGYVAE peptide
-
pH and temperature not specified in the publication
-
2.3e-07
-
rosuvastatin
-
37C, hepatocytes
3.1e-06
-
rosuvastatin
-
inhibition of purified enzyme
3.3e-05
-
SFGYVAE peptide
-
pH and temperature not specified in the publication
-
1.3e-06
-
simvastatin
-
37C, hepatocytes
4.9e-05
-
simvastatin
-
inhibition of purified enzyme
0.82
-
sodium (E,3R,5S)-7-(2-(2-fluorophenyl)-4-(3-phenylpentan-3-yl)phenyl)-3,5-dihydroxy-hept-6-enoate
-
DL-[3-14C]3-hydroxy-3-methylglutaryl-CoA (0.37 MBq) and 10 mg protein of microsomal fraction incubated at 37C for 30 min
1.2
-
sodium (E,3R,5S)-7-(2-(3-fluorophenyl)-4-(3-phenylpentan-3-yl)phenyl)-3,5-dihydroxy-hept-6-enoate
-
DL-[3-14C]3-hydroxy-3-methylglutaryl-CoA (0.37 MBq) and 10 mg protein of microsomal fraction incubated at 37C for 30 min
0.15
-
sodium (E,3R,5S)-7-(2-(4-fluorophenyl)-4-(3-phenylpentan-3-yl)phenyl)-3,5-dihydroxy-hept-6-enoate
-
DL-[3-14C]3-hydroxy-3-methylglutaryl-CoA (0.37 MBq) and 10 mg protein of microsomal fraction incubated at 37C for 30 min
0.85
-
sodium (E,3R,5S)-7-(2-phenyl-4-(3-phenylpentan-3-yl)phenyl)-3,5-dihydroxyhept-6-enoate
-
DL-[3-14C]3-hydroxy-3-methylglutaryl-CoA (0.37 MBq) and 10 mg protein of microsomal fraction incubated at 37C for 30 min
7.4
-
sodium (E,3R,5S)-7-(4-(3-(2-fluorophenyl)pentan-3-yl)-2-isopropylphenyl)-3,5-dihydroxyhept-6-enoate
-
DL-[3-14C]3-hydroxy-3-methylglutaryl-CoA (0.37 MBq) and 10 mg protein of microsomal fraction incubated at 37C for 30 min
92
-
sodium (E,3R,5S)-7-(4-(3-(3-fluorophenyl)pentan-3-yl)-2-isopropylphenyl)-3,5-dihydroxyhept-6-enoate
-
DL-[3-14C]3-hydroxy-3-methylglutaryl-CoA (3.7 MBq) and 10 mg protein of microsomal fraction incubated at 37C for 30 min
1.8
-
sodium (E,3R,5S)-7-(4-(3-phenylpentan-3-yl)-2-isopropylphenyl)-3,5-dihydroxyhept-6-enoate
-
DL-[3-14C]3-hydroxy-3-methylglutaryl-CoA (0.37 MBq) and 10 mg protein of microsomal fraction incubated at 37C for 30 min
0.00026
-
TFGYVAE peptide
-
pH and temperature not specified in the publication
-
0.00045
-
VFGYVAE peptide
-
pH and temperature not specified in the publication
-
0.0526
-
YAVE
-
-
0.044
-
YAVE peptide
-
pH and temperature not specified in the publication
-
0.0418
-
YVAE
-
-
0.041
-
YVAE peptide
-
pH and temperature not specified in the publication
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.0006
-
-, Q7YT62, Q7YT63
about, native cells
0.003
-
-
-
0.0147
-
-
-
0.0164
-
-
-
0.0335
-
-
-
0.69
-
-
native enzyme in cell extract soluble fraction
3.9
-
-
50C, mutant L403R/G404R/A406S
4.9
-
-
pH 5.5, 50C
4.9
-
-
50C, wild-type
17.5
-
-
50C, pH 5.5, recombinant enzyme
28
-
-
purified recombinant enzyme
60
-
-, Q7YT62, Q7YT63
recombinant Sf9 cells
7800
-
-
purified enzyme
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.7
6.3
-
reduction of (S)-3-hydroxy-3-methylglutaryl-CoA
6
-
-
reduction of (R,S)-mevaldehyde
6.5
-
-
(S)-3-hydroxy-3-methylglutaryl-CoA reduction
6.8
-
-
-
6.8
-
-
assay at
7
-
-
(R)-mevalonate oxidation
7.4
-
-, Q7YT62, Q7YT63
assay at
7.4
-
-
MOPS buffer
7.4
-
-
assay at
7.5
-
-
assay at
7.5
-
-
phosphate buffer
7.5
-
-
assay at
7.5
-
-
assay at
8
-
-
oxidative acylation of (R,S)-mevaldehyde
8.7
9.6
-
oxidation of (R)-mevalonate
9.5
-
-
oxidative acylation of (R,S)-mevaldehyde or mevalonate
9.5
-
-
acetoacetyl-coenzyme A thiolysis
10.5
-
-
acetoacetyl-coenzyme A synthesis
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
22
-
-
assay at room temperature
25
-
-
assay at
30
-
-
assay at
30
-
-
assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
about, acetoacetyl-coenzyme A synthesis and thiolysis
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.9
-
-
sequence calculation
6.14
-
Q1W675
sequence calculation
7.63
-
-
sequence calculation
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
Q1W675
high expression level
Manually annotated by BRENDA team
-
samples of patients with cardiovascular disorders
Manually annotated by BRENDA team
Q1W675
low expression level
Manually annotated by BRENDA team
Q1W675
subcutaneous, high expression level
Manually annotated by BRENDA team
-
unfertilized female flowers
Manually annotated by BRENDA team
-
genes LcHMG1 and LcHMG2 exhibit distinct expression patterns during litchi fruit development. LcHMG1 expression is highest in the early stage of fruit development, correlated with the high level of cell division. Absolute levels of LcHMG1 expression vary among fruits of different pheno- or genotypes, with expression in large-fruited types reaching higher levels for longer duration compared to that in small-fruited types. LcHMG2 is most highly expressed in the late stage of fruit development, in association with biosynthesis of isoprenoid compounds required for later cell enlargement
Manually annotated by BRENDA team
-
colon cancer cell line
Manually annotated by BRENDA team
Q1W675
high expression level
Manually annotated by BRENDA team
-
NCTC 2544 cells. HMG-CoA reductase and peroxisome proliferator-activated receptor alpha are involved in clofibrate-induced apoptosis in human keratinocytes
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
-
-
Manually annotated by BRENDA team
Q1W675
high expression level
Manually annotated by BRENDA team
Q1W675
medium expression level
Manually annotated by BRENDA team
-, Q5RZ62
strong expression
Manually annotated by BRENDA team
A0N0D3, -
weak expression
Manually annotated by BRENDA team
-
HMG-CoA reductase activity is higher in both female and male Nagase analbumimetic rats than in Sprague-Dwwley rats. Ovariectomy results in no significant changes in total hepatic HMG-CoA reductase in female Sprague-Dawley rats
Manually annotated by BRENDA team
-
modified HMG-CoA reductase and low density lipoprotein receptor regulation is deeply involved in age-related hypercholesterolemia
Manually annotated by BRENDA team
-
the enzyme is fully activated both in acute and in chronic thioacetamide-treated animals, while no modifications are detected in its KM and in its short-term regulatory enzymes
Manually annotated by BRENDA team
Q1W675
high expression level
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
HMG-CoA reductase activity is higher in both female and male Nagase analbumimetic rats than in Sprague-Dwwley rats. Ovariectomy results in no significant changes in total hepatic HMG-CoA reductase in female Sprague-Dawley rats; modified HMG-CoA reductase and low density lipoprotein receptor regulation is deeply involved in age-related hypercholesterolemia
-
Manually annotated by BRENDA team
Rattus norvegicus Wistar
-
-
-
Manually annotated by BRENDA team
Q1W675
medium expression level
Manually annotated by BRENDA team
Q1W675
low expression level
Manually annotated by BRENDA team
-, Q5RZ62
poor expression
Manually annotated by BRENDA team
A0N0D3, -
strong expression
Manually annotated by BRENDA team
Q1W675
longissimus, low expression level
Manually annotated by BRENDA team
-
from tail
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
from tail
-
Manually annotated by BRENDA team
Q1W675
low expression level
Manually annotated by BRENDA team
Q1W675
low expression level
Manually annotated by BRENDA team
Q1W675
low expression level
Manually annotated by BRENDA team
-, Q5RZ62
strong expression
Manually annotated by BRENDA team
A0N0D3, -
weak expression
Manually annotated by BRENDA team
Q1W675
low expression level
Manually annotated by BRENDA team
Q1W675
medium expression level
Manually annotated by BRENDA team
additional information
-, Q7YT62, Q7YT63
very low content in other tissues, higher enzyme activity in male organisms than in female, tissue distribution overview
Manually annotated by BRENDA team
additional information
-
growth at high and low salinity, quantitative expression analysis, overview, the expression of HMGR is regulated in response to non-optimal salinity in the halophilic archaeon
Manually annotated by BRENDA team
additional information
-
the activity of microsomal isoyzme Hmg2 is highest under hypo-saline and extremely hyper-saline conditions, and down-regulated under optimal growth conditions, while the activity of the truncated mitochondrial Hmg1 is constant under different growth conditions
Manually annotated by BRENDA team
additional information
-
analysis of LcHMG1 and LcHMG2 expressions in various litchi tissues, developmental stages and genotypes, overview. Expression of LcHMG1 and LcHMG2 is universally detected in all the tissues analyzed, including unfertilized female flowers, fruit tissues, leaves, shoots, and roots but their expression level appears to vary from tissue to tissue, with the highest expression found in the young pericarp (39 DAA) and the lowest in the aged seed. High level of expression in young tissues compared to aged tissues for a given organ except root
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
transmembrane protein
Manually annotated by BRENDA team
-
located on the cytoplasmic site, integrated into the membrane
Manually annotated by BRENDA team
-
localized predominantly within spherical vesicular structures that range from 0.0002-0.0006 mm in diameter, located in the cytoplasm and within the central vacuole in differentiated cotyledon cells. The N-terminal region, including the transmembrane domain of HMGR, is found to be necessary and sufficient for directing HMGR to the endoplasmic reticulum and the spherical structures
Manually annotated by BRENDA team
-, Q7YT62, Q7YT63
bound, isozyme HMGR2, about 25% of total enzyme content
Manually annotated by BRENDA team
-
transmembrane protein
Manually annotated by BRENDA team
-
a transmembrane enzyme
Manually annotated by BRENDA team
A0N0D3, -
contains two transmembrane domains
Manually annotated by BRENDA team
Mus musculus C57BL/6J, Rattus norvegicus Wistar
-
-
-
-
Manually annotated by BRENDA team
-, Q7YT62, Q7YT63
isozyme HMGR1, about 75% of total enzyme content
-
Manually annotated by BRENDA team
additional information
-
enzyme undergoes endoplasmic reticulum-associated degradation which is physiologically regulated by sterol pathway signals
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
11000
-
-
gel filtration
52000
56000
-
proteolytically cleaved soluble enzyme fragment
63000
-
-
immunoblot analysis, isoform HMGR1S
66000
-
-
gel filtration
72000
-
-, Q7YT62, Q7YT63
-
96000
-
-
intact membrane protein
100000
-
-
PAGE
100000
-
-
gel filtration
140000
-
-, Q7YT62, Q7YT63
isozyme HMGR1, minor peak, gel filtration
184000
-
-
gel filtration
200000
-
-
PAGE
217000
226000
-
gel filtration, ultracentrifugation
540000
-
-, Q7YT62, Q7YT63
isozyme HMGR1, major peak, gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 46000, SDS-PAGE
?
-
x * 54500, recombinant His-tagged catalytic domain, SDS-PAGE
?
-
x * 62400, about, sequence calculation
?
Q1W675
x * 97150, sequence calculation
dimer
-
alpha2, 2 * 41000, SDS-PAGE
dimer
-
2 * 97100, about, sequence calculation
dimer
-
alpha2, 2 * 41000, SDS-PAGE
-
monomer
-
1 * 11000, SDS-PAGE
oligomer
-, Q7YT62, Q7YT63
1 x 69000, recombinant His-tagged isozyme HMGR1, SDS-PAGE
tetramer
-
alpha4, 4 * 46000, SDS-PAGE
tetramer
-
-
monomer
-
1 * 66000, SDS-PAGE
additional information
-
homology modeling of the catalytic domain
additional information
-
JcHMGR has three domains: 1. the small, helical N-terminal N-domain, 2. the large, central L-domain harboring two HMG-CoA binding motifs EMPIGFLQIP and TTEGCLVA, and an NADP(H)-binding motif GTVGGGT, and 3. the small helical S-domain harboring an NADP(H)-binding motif characterized by the sequence DAMGMN
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phosphoprotein
-
activity is regulated by phosphorylation and dephosphorylation
phosphoprotein
-
regulation of the plant enzyme by phosphorylation/dephosphorylation
glycoprotein
-
the enzyme sequence contains a glycosylation site
phosphoprotein
-
the enzyme sequence contains a phosphorylation site
phosphoprotein
-
activity is regulated by phosphorylation and dephosphorylation
phosphoprotein
Rattus norvegicus Wistar
-
activity is regulated by phosphorylation and dephosphorylation
-
phosphoprotein
-
regulation of the plant enzyme by phosphorylation/dephosphorylation
glycoprotein
Q1W675
identification of five N-glycosylation sites
lipoprotein
Q1W675
identification of nineteen N-myristoylation sites and three characteristic sites
phosphoprotein
Q1W675
identification of a cAMP-and cGMP-dependent protein kinase phosphorylation site, thirteen Protein kinase C phosphorylation sites, and eleven Casein kinase II phosphorylation sites
phosphoprotein
-
activity is regulated by phosphorylation and dephosphorylation
additional information
-, Q7YT62, Q7YT63
the isozyme is not regulated by phosphorylation; the isozyme is probably not regulated by phosphorylation
glycoprotein
-
-
additional information
-
genistein, eicosapentaenoic acid and docosahexaenoic acid down-regulate reductase activity, primarily through posttranscriptional effects
proteolytic modification
-
proteolysis releases a soluble, active fragment of 52-56 kDa
additional information
-
ubiquitination and proteasomal degradation of microsomal, but not mitochondrial, HMGR isozymes depends on environmental salinity, overview
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
enzyme in complex with inhibitor lovastatin, from 1.2 M ammonium sulfate, at 20C, a few days, larger crystals by microseeding, complexing with the inhibitor by soaking in a KOH solution, pH 9.0, containing 2 mM lovastatin, X-ray diffraction structure determination and analysis at 2.6 A resolution
-
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
19
-
-
below 19C reversible inactivation of enzyme activity, prevented by NADPH and NADP+
90
-
-
half-life at 90C is 3.2 h; stable
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
presence of reduced thiol compounds is important for enzyme stability
-
freezing and thawing leads to a doubling of the activity
-
presence of reduced thiol compounds is important for enzyme stability
-
glycerol strongly stabilizes the enzyme, stabilization against endoplasmic reticulum-associated degradation
-
ORGANIC SOLVENT
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
dithiothreitol
-
10 mM at pH 7 reverses CoA disulfide inactivation of enzyme
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
0C, 24 h, 25% loss of activity
-
-10C, crude microsomal form, 10-20% loss of activity per week
-
-20C, after quick freezing in acetone/solid CO2 at -80C, one week, 10% loss of activity
-
-20C, crude enzyme, 30 days, no loss in activity
-
-20C, partially purified enzyme, 24-48 h, loss of most of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
recombinant His-tagged enzyme from Escherichia coli by nickel-affinity chromatography
-
native soluble isozyme HMGR1 from mandibular organ by ultracentrifugation, anion exchange chromatography, ultrafiltration and gel filtration, recombinant enzyme from Sf9 insect cells by nickel affinity chromatography
-, Q7YT62, Q7YT63
isozymes Hmg1 and Hmg2 partially by subcellular fractionation
-
recombinant His-tagged catalytic domain from Escherichia coli by nickel affinity chromatography
-
partially, preparation of microsomes and solubilization by trypsin
-
4380fold to homogeneity from microsomes by solubilization with trypsin, and affinity chromatography on 2',5'-ADP-resin and HMG-CoA-hexane resin
-
; recombinant enzyme
-
3.8fold, recombinant enzyme from Escherichia coli
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
overexpression of the HMGR gene in transgenic Artemisia annua plants using Agrobacterium-mediated gene transfer technology
-
expression in Escherichia coli strain DH5alpha as His-tagged enzyme
-
functional complementation of EuHMGR in HMGR-deficient mutant yeast JRY2394 demonstrates that EuHMGR mediates the mevalonate biosynthesis in yeast
-, Q5RZ62
expressed in Escherichia coli
A0N0D3, -
DNA and amino aid sequence determination and analysis, cloning in Escherichia coli and functional complementation of a HMGR-deficient mutant yeast strain using the yeast-Escherichia coli coli shuttle vector pYF1845
B2KX91
expression in Escherichia coli
-
gene hmgR, expression analysis under different salinity growth conditions, hmgR transcript increases in abundance with increasing salinity by a factor of 2.2fold
-
construction of a N-terminally truncated enzyme, comprising the catalytic site, and subcloning into Escherichia coli strain DH5alpha
-
isozyme HMGR1, DNA and amino acid sequence determination and analysis, functional expression in Spodoptera frugiperda Sf9 cells via baculovirus infection system as His-tagged enzyme; isozyme HMGR2, DNA and amino acid sequence determination and analysis
-, Q7YT62, Q7YT63
cDNA encoding the wild-type and mutant forms of human HMG-CoA reductase expressed under control of the yeast MET25 promoter in a Saccharomyces cerevisiae strain with deletions of both HMG1 and HMG2
-
gene hmgr, genomic DNA sequence and full-length cDNA, as well as JcHMGR amino acid sequence determination and analysis, phylogenetic analysis, expression in Escherichia coli strain Top 10F'
-
overexpression of the recombinant His-tagged enzyme in Lactococcus lactis strain NZ9000, co-expression with sesquiterpene synthase gene, PMSTS from Persicaria minor incorporated into the pNZ8048 plasmid, with two base substitutions, 796A.G and 1077A.G, introduced into the PMSTS gene during amplification resulting in exchange K266E and a silent mutation
-
overexpression in Escherichia coli
-
genes LcHMG1 and LcHMG2, DNA and amino acid sequence determination and analysis, real-time quantitative RT-PCR expression analysis
-
expression of the His-tagged catalytic domain of the enzyme, residues E416-F887, in Escherichia coli
-
expression in Escherichia coli
-
expression of c-myc-tagged enzyme from plasmid in yeast, expression as GFP-fusion protein
-
the HMG1-overexpressing episome (pRS434GAP-HMG1) introduced into 36 type strains purchased from ATCC, and yeast recombinant AURGG101
P12683
expression in Escherichia coli
-
overexpression in Escherichia coli
-
coexpression of the Sulfolobus solfataricus hmgA gene in Escherichia coli with the argU gene that encodes tRNAAGA,AGG results in an over 10fold increase in enzyme yield; expression in Escherichia coli
-
expression in Escherichia coli
-
DNA and amino acid sequence determination and analysis, sequence comparisons, RT-PCR and real-time PCR expression analysis
Q1W675
expression in Escherichia coli strain BL21(DE3) as soluble protein
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
A333P
P00347
mutation disrupts Insig binding and abolishes sterol-accelerated degradation. The pivotal event for sterol-induced degradation of the choletsreol biosynthetic enzyme HMG-CoA reductase is binding of its membrane domain to Insig proteins in the endoplasmic reticulum. Insig are carriers for gp78, an E3 ubiquitin ligase that marks reductase for proteasomal degradation
G87R
P00347
mutation disrupts Insig binding and abolishes sterol-accelerated degradation. The pivotal event for sterol-induced degradation of the choletsreol biosynthetic enzyme HMG-CoA reductase is binding of its membrane domain to Insig proteins in the endoplasmic reticulum. Insig are carriers for gp78, an E3 ubiquitin ligase that marks reductase for proteasomal degradation
Q766H
-
restores viability of Saccharomyces cerevisiae strains lacking the HMG1 and HMG2 genes, thus is catalytically active in yeast cells. Q766H mutation, which affects the structure of the catalytic domain, increases the sensitivity of the enzyme towards statin treatment
R393Q
-
restores viability of Saccharomyces cerevisiae strains lacking the HMG1 and HMG2 genes, thus is catalytically active in yeast cells. R393Q mutation does not change the properties of the enzyme towards statin treatment
R387S
-
regulation of activity by phosphorylation
L403R/G404R/A406S
-
engineering of an appropriately located phosphoacceptor serine and cAMP-dependent protein kinase recognition motif to create a phosphorylation site. Km values, Vmax, optimal pH and temperature of mutant are identical to wild-type. Exposure of mutant to ATP and cAMP-dependent protein kinase is accompanied by incorporation of phosphate and by a parallel decrease in catalytic activity. Subsequent treatment with a protein phosphatase releases enzyme-bound 32Pi and restores activity to pretreatment levels; regulation of activity by phosphorylation
synthesis
-
due to use of rare codon, expression of enzyme in Escherichia coli is poor. Coexpression of the S. solfataricus hmgA gene with the argU gene that encodes tRNAAGA,AGG resulted in an over 10-fold increase in enzyme yield
L498I
Q1W675
the naturally occuring mutation T1564C creates a c-Rel binding site
additional information
-
construction of insertion mutants of the 2 isozymes leads to loss of enzyme function, the hmg1 mutant plants show an altered phenotype with dwarfing, early senescence, male sterility, and both mutants of hmg1 and hmg2 show reduced sterol levels, the mutants are more sensitive to the inhibitor lovastatin and squalestatin, overview
additional information
-
transgenic expression of the N-terminal truncated 3-hydroxy-3-methylglutaryl CoA reductase from Arabidopsis thaliana in Lavandula latifolia plants enhances production of essential oils and sterols in the different lines of transgenic plants, expression of HMGR1S also increases the amount of the end-product sterols beta-sitosterol and stigmasterol by 1.8fold and 1.9fold, respectively, but does not affect the accumulation of carotenoids or chlorophylls, overview
S60N
P00347
mutation disrupts Insig binding and abolishes sterol-accelerated degradation. The pivotal event for sterol-induced degradation of the choletsreol biosynthetic enzyme HMG-CoA reductase is binding of its membrane domain to Insig proteins in the endoplasmic reticulum. Insig are carriers for gp78, an E3 ubiquitin ligase that marks reductase for proteasomal degradation
additional information
-
coexpression of N-terminal truncated Hevea brasiliensis (S)-3-hydroxy-3-methylglutaryl CoA reductase and tobacco C24-sterol methyltransferase type 1 in transgenic Nicotiana tabacum plants enhances carbon flux towards end-product sterols, expression under control of both seed-specific and constitutive promotors leads to enhancement of sterol accumulation by 2.5 and 2.1fold, respectively, analysis of the sterol spectrum, overview
additional information
-
expression of human HMG-CoA reductase in yeast complements the lethal phenotype of Saccharomyces cerevisiae strains lacking the HMG1 and HMG2 genes
M430T
Q1W675
naturally occuring mutation T1392C
additional information
Q1W675
identification of five single nucleotide polymorphisms, three of them are synonymous mutations and the other two are missense mutations, the naturally occuring mutation T1541C causes a deletion of a CdxA element and a C/EBP binding site and created a c-Ets-binding site, and naturally occuring mutation G973T in exon 9, which is a synonymous mutation
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
drug development
-
overexpression of HMGR appears promising for obtaining a constant high production of artemisinin, an effective drug against malaria for which no resistant strains of Plasmodium falciparum have been reported
drug development
-
a yeast expression system can serve to study the influence of selected mutations in human HMG-CoA reductase on the sensitivity of the enzyme to commonly prescribed statins, thus this model system is suitable for the development and selection of lipid-lowering drugs as well as for the examination of DNA sequence variations in the context of statin therapy
medicine
-
the enzyme is a target for intervention in the treatment of hypercholesterolaemia, clinical utility of inhibitors to decrease the levels of atherogenic lipiproteins in patients
medicine
-
genistein, eicosapentaenoic acid and docosahexaenoic acid down-regulate reductase activity, primarily through posttranscriptional effects. Diets rich in soy isoflavones and fish oils, therefore, may exert anti-cancer effects through the inhibition of mevalonate synthesis in the breast. Genistein and docosahexaenoic acid, in particular, may augment the efficacy of statins, increasing the potential for use of these drugs in adjuvant therapy for breast cancer
molecular biology
-
Lactococcus lactis is a potential heterologous host for the production of sesquiterpenes from a herbaceous Malaysian plant, Persicaria minor. A sesquiterpene synthase gene encoding beta-sesquiphellandrene synthase from Persicaria minor is successfully cloned and expressed in Lactococcus lactis. Overexpression of the Lactococcus lactis endogenous 3-hydroxy-3-methylglutaryl Co-A reductase, an established rate-limiting enzyme in the eukaryotic mevalonate pathway, increases the production level of beta-sesquiphellandrene by 1.25-1.60 fold
molecular biology
Lactococcus lactis NZ9000
-
Lactococcus lactis is a potential heterologous host for the production of sesquiterpenes from a herbaceous Malaysian plant, Persicaria minor. A sesquiterpene synthase gene encoding beta-sesquiphellandrene synthase from Persicaria minor is successfully cloned and expressed in Lactococcus lactis. Overexpression of the Lactococcus lactis endogenous 3-hydroxy-3-methylglutaryl Co-A reductase, an established rate-limiting enzyme in the eukaryotic mevalonate pathway, increases the production level of beta-sesquiphellandrene by 1.25-1.60 fold
-
drug development
-
inhibitors of HMG-CoA reductase for reducing low density lipoprotein cholesterol in the treatment of hypercholesterolemia
medicine
-
dual therapy with the HMG-CoA reductase inhibitor pravastatin and the angiotensin receptor antagonist olmesartan, which produce an additive reduction in cardiomyocyte hypertrophy and cardiac fibrosis after myocardial infarction through different mechanisms, decreases the propensity of the heart to arrhythmogenesis
medicine
P51639
the cholesterol absorption inhibitor ezetimibe profoundly lowers serum cholesterol levels in animals expressing very low rates of hepatic cholesterol synthesis and produces large compensatory increases in hepatic HMG-CoA reductase expression without signifucantly affecting expression of hepatic low density lipoprotein receptors. This indicates that ezitimibe should be most effective in lowering serum cholesterol levels in peaple with low rates of cholesterol synthesis/High rates of cholesterol absorption
medicine
-
treatment with the inhibitor atorvastatin exerts early nephroprotective effects in a rat model of chronic inhibition of nitric axide synthesis
biotechnology
P12683
overexpression of HMG1 is the most effective among all other genes in both hosts Saccharomyces cerevisiae ATCC 200589 and ATCC 76625 for prenyl alcohol production