1887

Abstract

A gene encoding 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase was isolated from the maize fungal pathogen . This was accomplished by identifying cDNA and genomic clones that hybridized to an internal fragment of the gene, amplified from genomic DNA by PCR. The nature of the gene was determined by nucleotide sequence analysis, and by comparing the derived amino acid sequence of the gene with HMG-CoA reductases from yeast, and from other organisms. The hydrophobic nature of the N-terminal region of the deduced protein sequence also supported the view that this gene encoded HMG-CoA reductase. A C-terminal-truncated fragment of the HMG-CoA reductase gene was shown to be expressed in in a catalytically active form. The expressed protein was also shown to be sensitive to an inhibitor of mammalian HMG-CoA reductase activity.

Loading

Article metrics loading...

/content/journal/micro/10.1099/13500872-140-9-2363
1994-09-01
2022-01-20
Loading full text...

Full text loading...

/deliver/fulltext/micro/140/9/mic-140-9-2363.html?itemId=/content/journal/micro/10.1099/13500872-140-9-2363&mimeType=html&fmt=ahah

References

  1. Anderson R.G.W., Orci L, Brown M. S., Garcia-Segura L. M., Goldstein J. L. 1983; Ultrastructural analysis of crystalloid endoplasmic reticulum in UT-1 cells and its disappearance in response to cholesterol. J Cell Sci 63:1–20
    [Google Scholar]
  2. Bach T.J. 1987; Synthesis and metabolism of mevalonic acid in plants. PI Physiol Biochem 25:163–178
    [Google Scholar]
  3. Bailey A. M., Burden R. S., James C. S., Keon J. P. R., Croxen R., Bard M., Hargreaves J. A. 1994; Isolation, characterization and sequence of a gene conferring resistance to the systemic fungicide carboxin from the maize smut pathogen, Ustilago maydis. Exp My col 18:87–92
    [Google Scholar]
  4. Baldwin B.C. 1989; Inhibitors of ergosterol biosynthesis as crop protection agents. Biochem Soc Trans 18:61–62
    [Google Scholar]
  5. Ballance D.J. 1991; Transformation systems for filamentous fungi and an overview of fungal gene structure. In Molecular Industrial Mycology: Systems and Applications for Filamentous Fungi pp. 1–29 Edited by Leong S. A., Berka R. M. New York: Marcel Dekker;
    [Google Scholar]
  6. Basson M. E., Thorsness M., Rine J. 1986; Saccharomyces cerevisiae contains two functional genes encoding 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Proc Natl Acad Sci USA 83:5563–5567
    [Google Scholar]
  7. Basson M. E., Thorsness M., Finer-moore J., Stroud R. M., Rine J. 1988; Structural and functional conservation between yeast and human 3-hydroxy-3-methylglutaryl coenzyme A reductases: the rate-limiting enzyme of sterol biosynthesis. Mol Cell Biol 8:3797–3808
    [Google Scholar]
  8. Beach M.J., Rodwell V. W. 1989; Cloning, sequencing, and overexpression of mva A, which encodes Pseudomonas mevalonii 3-hydroxv-3-methylglutaryl coenzvme A reductase.. J Bacterial 171:2994–3001
    [Google Scholar]
  9. Burmester A., Czempinski K. 1994; Sequence comparison of a segment of the gene for 3-hydroxy-3-methylglutaryl-coenzyme A reductase in zygomycetes. Em J Biochem 220:403–408
    [Google Scholar]
  10. Clarke P.R., Hardie D. G. 1990; Regulation of HMG-CoA reductase: identification of the site phosphorylated by the AMP-activated protein kinase in vitro and in intact rat liver.. EMBO J 9:2439–2446
    [Google Scholar]
  11. Darnay B.G., Rodwell V. W. 1993; His865 is the catalytically important histidyl residue of Syrian hamster 3-hydroxy-3-methylglutaryl-coenzyme A reductase. J Biol Chem 268:8429 –8435
    [Google Scholar]
  12. Darnay B. G., Wang Y., Rodwell V. W. 1992; Identification of the catalytically important histidine of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. J Biol Chem 267:15064–15070
    [Google Scholar]
  13. Edwards P.A., Fogelman A. M. 1985; Studies on purified mammalian HMG-CoA reductase and regulation of enzyme activity. In Regulation of HMG-CoA Reductase pp. 133–148 Edited by Preiss B. Orlando, FL: Academic Press;
    [Google Scholar]
  14. Endo A. 1985; Specific nonsterol inhibitors of HMG-CoA reductase. In Regulation of HMG-CoA Reductase pp. 49–78 Edited by Preiss B. Orlando, FL: Academic Press;
    [Google Scholar]
  15. Ferrer A., Aparicio C., Nogues N., Wettstein A., Bach T. J., Boronat A. 1990; Expression of catalytically active radish 3-hydroxy-3-methylglutaryl-coenzyme A reductase in Escherichia coli.. FEBS Lett 266:67–71
    [Google Scholar]
  16. Frimpong K., Rodwell V. W. 1994; Catalysis by syrian hamster 3-hydroxy-3-methylglutaryl-coenzyme A reductase: proposed roles of histidine 865, glutamate 558 and aspartate 766. J Biol Chem 259:11478–11483
    [Google Scholar]
  17. Frimpong K., Darney B. G., Rodwell V. W. 1993; Syrian hamster 3-hydroxy-3-methylglutaryl-coenzyme A reductase expressed in Escherichia coli:. production of homologous protein.. Protein Expression Purif 4:337–344
    [Google Scholar]
  18. Gil G., Faust J. R., Chin D. J., Goldstein J. L., Brown M. S. 1985; Membrane-bound domain of HMG-CoA reductase is required for sterol-enhanced degradation of the enzyme. Cell 41:249–258
    [Google Scholar]
  19. Gillespie J.G., Hardie D. G. 1992; Phosphorylation and inactivation of HMG-CoA reductase at the AMP-activated protein kinase site in response to fructose treatment of isolated rat hepatocytes. FEBS Lett 306:59–62
    [Google Scholar]
  20. Goldstein J.L., Brown M. S. 1990; Regulation of the mevalonate pathway. Nature 343:425–430
    [Google Scholar]
  21. Gurr S. J., Unkles S. E., Kinghorn J. R. 1987; The structure and organization of nuclear genes of filamentous fungi. In Gene Structure in Eukaryotic Microbes pp. 93–139 Edited by Kinghorn J.R. Oxford and Washington: IRL Press;
    [Google Scholar]
  22. Hargreaves J.A., Turner G. 1989; Isolation of the acetyl-CoA synthetase gene from the corn smut pathogen, Ustilago maydis. J Gen Microbiol 135:2675–2678
    [Google Scholar]
  23. Ikeura R., Murakawa S., Endo A. 1988; Growth inhibition of yeast by compactin (ML-236B) analogues. J Antibiot 41:1148–1150
    [Google Scholar]
  24. Jingami H., Brown M. S., Goldstein J. L., Anderson R. G. W., Luskey K. L. 1987; Partial deletion of membrane-bound domain of 3-hydroxy-3-methylglutaryl coenzyme A reductase eliminates sterol-enhanced degradation and prevents formation of crystalloid endoplasmic reticulum. J Cell Biol 104:1693–1704
    [Google Scholar]
  25. Kelly S. L., Kenna S., Bligh H. F. J., Watson P. F., Stansfield I., Ellis S.W., Kelly D. E. 1990; Lanosterol to ergosterol -enzymology, inhibition and genetics. In Biochemistry of Cell Walls and Membranes in Fungi pp. 223–243 Edited by Kuhn P. J., Trinci A. P. J. , Jing M. J., Goosey M. W. , Copping L. G. . Berlin: Springer-V erlag;
    [Google Scholar]
  26. Keon J.P.R., White G. A., Hargreaves J. A. 1991; Isolation, characterization and sequence of a gene conferring resistance to the systemic fungicide carboxin from the maize smut pathogen, Ustilago maydis. Curr Genet 19:475–481
    [Google Scholar]
  27. Koller W. 1992; Antifungal agents with target sites in sterol functions and biosynthesis. In Target Sites of Fungicide Action pp. 191–206 Edited by Koller W. Boca Raton, FL: CRC Press;
    [Google Scholar]
  28. Kyte J., Doolittle R. F. 1982; A simple method for displaying the hydropathic character of a protein. J Mol Biol 157:105–132
    [Google Scholar]
  29. Laemmli U.K. 1970; Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685
    [Google Scholar]
  30. Learned R.M., Fink G. R. 1989; 3-Hydroxy-3-methylglutaryl-coenzyme A reductase from Arabidopsis thaliana is structurally distinct from the yeast and animal enzymes.. Proc Natl Acad Sci USA 86:2779–2783
    [Google Scholar]
  31. Marriott M.S. 1990; The rational design of fungal lanosterol Cl 4 demethylase inhibitors. In Molecular Aspects of Chemotherapy pp. 193–204 Edited by Borowski E., Shugar D. . New York: Pergamon Press;
    [Google Scholar]
  32. Nakanishi M., Goldstein J. L., Brown M. S. 1988; Multivalent control of 3-hydroxy-3-methylglutaryl coenzyme A reductase: mevalonate-derived product inhibits translation of mRNA and accelerates degradation of enzyme. J Biol Chem 263:8929–8937
    [Google Scholar]
  33. Olender E.H., Simoni R. D. 1992; The intracellular targeting and membrane topology of 3-hydroxy-3-methylglutaryl-CoA reductase. J Biol Chem 267:4223–4235
    [Google Scholar]
  34. Osborne T.F. 1991; Single nucleotide resolution of sterol regulatory region in promoter for 3-hydroxy-3-methylglutaryl coenzyme A reductase. J Biol Chem 266:13947–13951
    [Google Scholar]
  35. Panini S. R., Rogers D. H., Rudney H. 1985; Regulation of HMG-CoA reductase and the biosynthesis of nonsteroid prenyl derivatives. In Regulation of HMG-CoA Reductase pp. 149–181 Edited by Preiss B. Orlando, FL: Academic Press;
    [Google Scholar]
  36. Pearson W.R., Lipman D. J. 1988; Improved tools for biological sequence comparison. Proc Natl Acad Sci USA 85:2444–2448
    [Google Scholar]
  37. Preiss B. 1985 Regulation of HMG-CoA Reductase. Orlando, FL: Academic Press;
    [Google Scholar]
  38. Reynolds G. A., Basu S. K., Osborne T. F., Chin D. J., Gil G., Brown M. S., Goldstein J. L., Luskey K. L. 1984; HMG-CoA reductase: a negatively regulated gene with unusual promoter and 5' untranslated regions. Cell 38:275–285
    [Google Scholar]
  39. Roitelman J., Olender E. H., Bar-nun S., Dunn W. A., Simoni R. D. 1992; Immunological evidence for eight spans in the membrane domain of 3-hydroxy-3-methylglutaryl coenzyme A reductase: implications for enzyme degradation in the endoplasmic reticulum. J Cell Biol 117:959–973
    [Google Scholar]
  40. Sambrook J., Fritsch E. F., Maniatis T. 1989 Molecular Cloning: a Eaboratory Manual 2nd end Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  41. Sanger F., Nicklen S., Coulson A. R. 1977; DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 74:5463–5467
    [Google Scholar]
  42. Sato R., Goldstein J. L., Brown M. S. 1993; Replacement of serine-871 of hamster 3-hydroxy-3-methylglutaryl-CoA reductase prevents phosphorylation by AMP-activated kinase and blocks inhibition of sterol synthesis induced by ATP depletion. Proc Natl Acad Sci USA 90:9261–9265
    [Google Scholar]
  43. Sengstag C., Stirling C., Schekman R., Rine J. 1990; Genetic and biochemical evaluation of eucaryotic membrane protein topology: multiple transmembrane domains of Saccharomyces cerevisiae 3-hydroxy-3-methylglutaryl coenzyme A reductase. Mol Cell Biol 10:672–680
    [Google Scholar]
  44. Sinensky M., Lutz R. J. 1992; The prenylation of proteins. Bio Essays 14:25–31
    [Google Scholar]
  45. Skalnik D.G., Simoni R. D. 1985; The nucleotide sequence of the Syrian hamster HMG-CoA reductase. DNA 4:439–444
    [Google Scholar]
  46. Stutz A. 1990; Allylamine derivatives -inhibitors of fungal squalene epoxidase. In Molecular Aspects of Chemotherapy pp. 205–213 Edited by Borowski E., Shugar D. New York: Pergamon Press;
    [Google Scholar]
  47. Unkles S.E. 1992; Gene organization in industrial filamentous fungi. In Applied Molecular Genetics of Filamentous Fungi pp. 28–53 Edited by Kinghorn J. R., Turner G. . London and Glasgow: Blackie Academic and Professional;
    [Google Scholar]
  48. Wang Y., Darney B. G., Rodwell V. W. 1990; Identification of the principal catalytically important acidic residue of 3-hydroxy-3-methylglutaryl coenzyme A reductase. J Biol Chem 265:21634–21641
    [Google Scholar]
  49. Wright R., Basson M., D'ari L., Rine J. 1988; Increased amounts of HMG-CoA reductase induce ‘Karmellae’: a proliferation of stacked membrane pairs surrounding the yeast nucleus. J Cell Biol 107:101–114
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/13500872-140-9-2363
Loading
/content/journal/micro/10.1099/13500872-140-9-2363
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error