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Literature summary extracted from

  • Schwarz, B.H.; Driver, J.; Peacock, R.B.; Dembinski, H.E.; Corson, M.H.; Gordon, S.S.; Watson, J.M.
    Kinetic characterization of an oxidative, cooperative HMG-CoA reductase from Burkholderia cenocepacia (2014), Biochim. Biophys. Acta, 1844, 457-464.
    View publication on PubMed

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.1.1.88 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

EC Number Inhibitors Comment Organism Structure
1.1.1.88 simvastatin acid inhibitory as lactone or in as free aid Burkholderia cenocepacia
1.1.1.88 simvastatin lactone inhibitory as lactone or in as free aid Burkholderia cenocepacia

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
1.1.1.88 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
1.1.1.88 0.072
-
 NADH pH and temperature not specified in the publication Burkholderia cenocepacia
1.1.1.88 0.078
-
 (S)-3-hydroxy-3-methylglutaryl-CoA pH and temperature not specified in the publication Burkholderia cenocepacia

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
1.1.1.88 48000
-
-
 Burkholderia cenocepacia
1.1.1.88 118000
-
 gel filtration Burkholderia cenocepacia

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.1.1.88 (R)-mevalonate + CoA + 2 NAD+ Burkholderia cenocepacia
-
 (S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
-
 r

Organism

EC Number Organism UniProt Comment Textmining
1.1.1.88 Burkholderia cenocepacia B4EKH5
-
-

Posttranslational Modification

EC Number Posttranslational Modification Comment Organism
1.1.1.88 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 (Commentary)

EC Number Purification (Comment) Organism
1.1.1.88 recombinant His6-tagged enzyme by nickel affinity chromatography and gel filtration Burkholderia cenocepacia

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.1.1.88 (R)-mevalonate + CoA + 2 NAD+
-
 Burkholderia cenocepacia (S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
-
 r
1.1.1.88 (R)-mevalonate + CoA + 2 NAD+ NAD(H) is the preferred cofactor Burkholderia cenocepacia (S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
-
 r
1.1.1.88 additional information the substrates of the reductive reaction, HMG-CoA and NADH, both demonstrate sigmoidal behavior typical of positive cooperativity Burkholderia cenocepacia ?
-
 ?

Subunits

EC Number Subunits Comment Organism
1.1.1.88 homotrimer 3 * 48000, recombinant His6-tagged enzyme, SDS-PAGE, 3 * 47458, sequence calculation and mass spectrometry Burkholderia cenocepacia
1.1.1.88 More the enzyme might exist as trimer, and forms oligomers of trimers, overview Burkholderia cenocepacia

Synonyms

EC Number Synonyms Comment Organism
1.1.1.88 3-hydroxy-3-methylglutaryl coenzyme A reductase
-
 Burkholderia cenocepacia
1.1.1.88 HMG-CoA reductase
-
 Burkholderia cenocepacia
1.1.1.88 HMGR
-
 Burkholderia cenocepacia

Cofactor

EC Number Cofactor Comment Organism Structure
1.1.1.88 additional information the enzyme prefers NAD(H) over NADP(H) as a cofactor, suggesting an oxidative physiological role for the enzyme Burkholderia cenocepacia
1.1.1.88 NAD+
-
 Burkholderia cenocepacia
1.1.1.88 NADH
-
 Burkholderia cenocepacia

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
1.1.1.88 0.19
-
 pH and temperature not specified in the publication Burkholderia cenocepacia simvastatin lactone
1.1.1.88 90
-
 pH and temperature not specified in the publication Burkholderia cenocepacia simvastatin acid

General Information

EC Number General Information Comment Organism
1.1.1.88 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
1.1.1.88 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