Cloned (Comment) | Organism |
---|---|
BcHMGR is encoded by a gene between bases 588787 and 590073 on chromosome 2 of the Burkholderia cenocepacia genome, severe rare codon issues occur resulting in truncation products at 23 kD and 35 kD in addition to the expected size of 47.3 kD, successful recombinant expression of His6-tagged enzyme in Escherichia coli | Burkholderia cenocepacia |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
simvastatin acid | inhibitory as lactone or in as free aid | Burkholderia cenocepacia | |
simvastatin lactone | inhibitory as lactone or in as free aid | Burkholderia cenocepacia |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | kinetic analysis, overview. The enzyme exhibits positive cooperativity toward the substrates of the reductive reaction, but the oxidative reaction exhibits unusual double-saturation kinetics, distinctive among characterized HMG-CoA reductases. The unusual kinetics may arise from the presence of multiple active oligomeric states, each with different Vmax values | Burkholderia cenocepacia | |
0.072 | - |
NADH | pH and temperature not specified in the publication | Burkholderia cenocepacia | |
0.078 | - |
(S)-3-hydroxy-3-methylglutaryl-CoA | pH and temperature not specified in the publication | Burkholderia cenocepacia |
Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
---|---|---|---|
48000 | - |
- |
Burkholderia cenocepacia |
118000 | - |
gel filtration | Burkholderia cenocepacia |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
(R)-mevalonate + CoA + 2 NAD+ | Burkholderia cenocepacia | - |
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+ | - |
r |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Burkholderia cenocepacia | B4EKH5 | - |
- |
Posttranslational Modification | Comment | Organism |
---|---|---|
additional information | some minor oxidation of Met residues is detected in the trypsin-digested protein, particularly at Met343 and Met345, but no other significant post-translational modification of the enzyme could be detected | Burkholderia cenocepacia |
Purification (Comment) | Organism |
---|---|
recombinant His6-tagged enzyme by nickel affinity chromatography and gel filtration | Burkholderia cenocepacia |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
(R)-mevalonate + CoA + 2 NAD+ | - |
Burkholderia cenocepacia | (S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+ | - |
r | |
(R)-mevalonate + CoA + 2 NAD+ | NAD(H) is the preferred cofactor | Burkholderia cenocepacia | (S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+ | - |
r | |
additional information | the substrates of the reductive reaction, HMG-CoA and NADH, both demonstrate sigmoidal behavior typical of positive cooperativity | Burkholderia cenocepacia | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
homotrimer | 3 * 48000, recombinant His6-tagged enzyme, SDS-PAGE, 3 * 47458, sequence calculation and mass spectrometry | Burkholderia cenocepacia |
More | the enzyme might exist as trimer, and forms oligomers of trimers, overview | Burkholderia cenocepacia |
Synonyms | Comment | Organism |
---|---|---|
3-hydroxy-3-methylglutaryl coenzyme A reductase | - |
Burkholderia cenocepacia |
HMG-CoA reductase | - |
Burkholderia cenocepacia |
HMGR | - |
Burkholderia cenocepacia |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
additional information | the enzyme prefers NAD(H) over NADP(H) as a cofactor, suggesting an oxidative physiological role for the enzyme | Burkholderia cenocepacia | |
NAD+ | - |
Burkholderia cenocepacia | |
NADH | - |
Burkholderia cenocepacia |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.19 | - |
pH and temperature not specified in the publication | Burkholderia cenocepacia | simvastatin lactone | |
90 | - |
pH and temperature not specified in the publication | Burkholderia cenocepacia | simvastatin acid |
General Information | Comment | Organism |
---|---|---|
evolution | a key enzyme in endogenous cholesterol biosynthesis in mammals and isoprenoid biosynthesis via the mevalonate pathway in other eukaryotes, archaea and some eubacteria | Burkholderia cenocepacia |
physiological function | the enzyme prefers NAD(H) over NADP(H) as a cofactor, suggesting an oxidative physiological role for the enzyme. Also, the Burkholderia cenocepacia genome lacks the genes for the downstream enzymes of the mevalonate pathway, but the organism clearly possesses the genes for all the DXP pathway enzymes, further supporting a nonreductive, non-biosynthetic role for BcHMGR | Burkholderia cenocepacia |