Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2004 Apr;186(7):1927-32.
doi: 10.1128/JB.186.7.1927-1932.2004.

Class II 3-hydroxy-3-methylglutaryl coenzyme A reductases

Matija Hedl  1 , Lydia Tabernero, Cynthia V Stauffacher, Victor W Rodwell
Affiliations
Review

Class II 3-hydroxy-3-methylglutaryl coenzyme A reductases

Matija Hedl et al. J Bacteriol. 2004 Apr.
No abstract available

PubMed Disclaimer

Figures

FIG. 1.
FIG. 1.
Intermediates and enzymes of the mevalonate pathway of isopentenyl diphosphate biosynthesis.
FIG. 2.
FIG. 2.
Reaction mechanism proposed for P. mevalonii HMG-CoA reductase. The three stages of the reaction and the roles proposed for the catalytic residues Lys267, Asp283, Glu83, and His381 (23) are shown.
FIG. 3.
FIG. 3.
Partial sequence alignments of four class I and four class II HMG-CoA reductases. Sequences were aligned by using T-COFFEE (www.expasy.ch). The regions selected include the catalytic glutamate, lysine, aspartate and histidine residues, which are indicated by a green background. Amino acids with a black background are identical for both classes of enzymes. Amino acids identical in the class I enzymes and in the class II enzymes are indicated by blue and red backgrounds, respectively. Abbreviations: S. sol, Sulfolobus solfataricus; S. cer, Saccharomyces cerevisiae (yeast); M. aur, Mesocricetus auratus (Syrian hamster); H. sap, Homo sapiens (human); S. aur, Staphylococcus aureus; E. fae, Enterococcus faecalis; A. ful, Archaeoglobus fulgidus; P. mev, Pseudomonas mevalonii.
FIG. 4.
FIG. 4.
Ribbon diagram of the HMG-CoA reductase homodimer with HMG-CoA and NAD+ bound. This view looks directly into the active-site cavity located at the interface between the two monomers, colored red and gray. The third or flap domain of the red monomer, colored yellow, closes over the active site when substrates bind. The flap domain has three helical segments (designated 1 to 3) that extend from residue 375 to the C-terminal residue 428. The flap domain of the gray monomer lies behind and thus is not visible. HMG-CoA and NAD+ are shown as stick models (green = C; blue = N; red = O; gray = P; yellow = S). Both the substrate and the cofactor bind in an extended conformation, HMG-CoA to the large domain of the red monomer and NAD+ to the small domain of the gray monomer. Reproduced by permission from reference (copyright 1999, National Academy of Sciences).
FIG. 5.
FIG. 5.
Ribbon diagrams of the active site for complexes of the class II HMG-CoA reductase of P. mevalonii with NAD+ and HMG-CoA (A), NADH and mevalonate (B), and lovastatin (C). Both substrates and coenzymes bind in an extended conformation between the two monomers. HMG-CoA and mevalonate bind to the large domain of one monomer, and NAD(H) binds to the small domain of the other monomer. Mevalonate binds in an extended conformation and occupies the same position as the HMG moiety of HMG-CoA. The nicotinamide ring of a coenzyme approaches the substrate in an orientation that facilitates hydride transfer. The interactions of lovastatin (C) mimic substrate binding in the central portion of the active-site cavity. Two water molecules (w1 and w2) mediate interactions with active-site residues. Hydrogen bond interactions are represented by dotted lines. The data for this figure appear in references and .
See this image and copyright information in PMC

References

    1. Bischoff, K. M., and V. W. Rodwell. 1996. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase from Haloferax volcanii: purification, characterization, and expression in Escherichia coli. J. Bacteriol. 178:19-23. - PMC - PubMed
    1. Bochar, D. A., J. A. Friesen, C. V. Stauffacher, and V. W. Rodwell. 1999. Biosynthesis of mevalonic acid from acetyl-CoA, p. 15-44. In D. Cane (ed.), Comprehensive natural products chemistry, vol. 2. Isoprenoids, including carotenoids and steroids. Pergamon Press, Oxford, United Kingdom.
    1. Bochar, D. A., C. V. Stauffacher, and V. W. Rodwell. 1999. Sequence comparisons reveal two classes of 3-hydroxy-3-methyl coenzyme A reductase. Mol. Genet. Metab. 66:122-127. - PubMed
    1. Bochar, D. A., C. V. Stauffacher, and V. W. Rodwell. 1999. Investigation of the conserved lysines of Syrian hamster 3-hydroxy-3-methylglutaryl coenzyme A reductase. Biochemistry 38:15848-15852. - PubMed
    1. Bochar, D. A., L. Tabernero, C. V. Stauffacher, and V. W. Rodwell. 1999. Aminoethylcysteine can replace the active site lysine of Pseudomonas mevalonii 3-hydroxy-3-methylglutaryl coenzyme A reductase. Biochemistry 38:8879-8883. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources