1.1.1.34: hydroxymethylglutaryl-CoA reductase (NADPH)

This is an abbreviated version, for detailed information about hydroxymethylglutaryl-CoA reductase (NADPH), go to the full flat file.

Reaction

(R)-mevalonate
+
CoA
+ 2 NADP+ =
(S)-3-hydroxy-3-methylglutaryl-CoA
+ 2 NADPH + 2 H+

Synonyms

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 coenzyme A reductase, 3-hydroxy-3-methylglutaryl coenzyme A reductase 1, 3-hydroxy-3-methylglutaryl-CoA reductase, 3-hydroxy-3-methylglutaryl-CoA reductase (NADPH), 3-hydroxy-3-methylglutaryl-coenzyme A reductase, 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, HMG CoA reductase, HMG-CoA reductase, HMG-CoAR, HMG1, HMG2, HMG2.2, Hmg2p, HMG3.3, HMGCoA reductase, HMGCoA reductase-mevalonate:NADP-oxidoreductase (acetylating CoA), HMGCoAR, HMGCR, HMGR, HMGR1, HMGR1S, HMGR2, hydroxy-3-methylglutoryl-Coenzyme A reductase, 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

ECTree

     1 Oxidoreductases
         1.1 Acting on the CH-OH group of donors
             1.1.1 With NAD+ or NADP+ as acceptor
                1.1.1.34 hydroxymethylglutaryl-CoA reductase (NADPH)

Engineering

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

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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A333P
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
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
S60N
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
the naturally occuring mutation T1564C creates a c-Rel binding site
M430T
naturally occuring mutation T1392C
additional information