Inhibition of the class II HMG-CoA reductase of Pseudomonas mevalonii.

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Hedl M, Rodwell VW

Inhibition of the class II HMG-CoA reductase of Pseudomonas mevalonii.

Protein Sci. 2004 Jun;13(6):1693-7.

PubMed ID

15152097 [ View in PubMed

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Abstract

There are two structural classes of HMG-CoA reductase, the third enzyme of the mevalonate pathway of isopentenyl diphosphate biosynthesis-the Class I enzymes of eukaryotes and the Class II enzymes of certain eubacteria. Structural requirements for ligand binding to the Class II HMG-CoA reductase of Pseudomonas mevalonii were investigated. For conversion of mevalonate to HMG-CoA the -CH(3), -OH, and -CH(2)COO(-) groups on carbon 3 of mevalonate were essential for ligand recognition. The statin drug Lovastatin inhibited both the conversion of HMG-CoA to mevalonate and the reverse of this reaction. Inhibition was competitive with respect to HMG-CoA or mevalonate and noncompetitive with respect to NADH or NAD(+). K(i) values were millimolar. The over 10(4)-fold difference in statin K(i) values that distinguishes the two classes of HMG-CoA reductase may result from differences in the specific contacts between the statin and residues present in the Class I enzymes but lacking in a Class II HMG-CoA reductase.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
NADH	3-hydroxy-3-methylglutaryl-coenzyme A reductase	Protein	Humans	Unknown	Not Available	Details