Dr. W. David Nes
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Title: |
Paul Whitfield Horn Professor |
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Education: |
Ph.D., University of Maryland, 1979; Postdoctoral Study, NIH Postdoctoral Fellow, University of California, Berkeley |
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Research Area: |
Biochemistry and Natural Products |
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Office: |
Chemistry 413-C |
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Principal Research Interests
- Natural Product Isolation
- Mechanistic Enzymology
- Cloning/Expression of Sterol Genes
The research of Professor Nes is concerned with the study of the biochemistry and molecular biology of phytosterols (including fungal sterols) and other natural products. Phytosterols are essential components of life. Professor Nes is interested in the evolution of sterol asymmetry and specificity in nature. The central dogma for sterol chemists is: what specific features of sterol structure are special in growth, differentiation and reproduction and what biochemical and physiological factors promote and/or limit transformations in sterol structure? To this end, Professor Nes has been studying the relationship between function and ecology of phytosterols and of protein structure and function of enzymes that control carbon flux through the phytosterol pathways of biological systems that range from the cyanobacteria to tracheophytes and in plant pests and pathogens. Multidisciplinary training of post-doctoral associates, graduate and undergraduate students is tripartate and involves:
- Bioorganic and radiotracer synthesis, natural product isolation and characterization using modern chromatographic and spectroscopic techniques;
- Cloning, sequencing, expression and purification of proteins, followed up with studies on mechanistic enzymology, and
- Structure/function studies using whole cell model systems and pulse/chase experiments to study sterol sequencing in phytosterol turnover.
Professor Nes has discovered that phytosterols differ from animal and insect sterols in that plants possess the ability to methylate the sterol side chain at carbon-24. This unique biochemical difference in phytosterol structure has been shown to be of commercial value in both the development of transgenic plants that possess broad-based insect resistance and the rational design of sterol methylation inhibitors that can function as taxa-specific antifungal agents.
Representative Publications
- "Effect of Substrate Features and Mutagenesis of Active Site tyrosine Residues on the Reaction Course Catalyzed by Trypanosoma brucei Sterol C24-Methyltransferase", Liu, J.; Ganapathy, K.; Wywial, E.; Bujnicki, J. M.; Nwogwugwu, C. A.; Nes, W. D. Biochem. J. 2011, 439, 413-422.
- "Substrate Preferences and Catalytic Parameters Determined by Structural Characteristics of Sterol 14a-Demethylase CYP51 from Leishmania infantum", Hargrove, T. Y.; Liu, J.; Nes, W. D.; Waterman, M. R.; Lepesheva. G. I. J. Biol. Chem. 2011, 286, 26838-26848.
- "Biosynthesis of Cholesterol and Other Sterols", Nes, W. D. Chem. Rev. 2011, 111, 6423-6451.
- "Purification, Characterization, and Inhibition of Sterol C24-Methyltransferase from Candida albicans", Ganapathy, K.; Kanagasabai, R.; Nguyen, T. T. M.; Nes, W. D. Arch. Biochem. Biophys. 2011, 505, 194-201.
- "Mechanism of Binding of Prothioconazole to Mycosphaerella graminicola CYP51 Differs from that of Other Azole Antifungals", Parker, J. E.; Warrilow, A. G. S; Cools, H. J.; Martel, C. M.; Nes, W. D.; Fraije, B. A.; Lucas, J. A.; Kelly, D. A.; Kelly. S. L. Appl. Environ. Microbiol. 2011, 77, 1460-1465.
- "Metabolic Engineering of Soybean Affords Improved Phytosterol Seed Traits", Neelakanda, A.; Valliyodan, B.; Chamala, S.; Nes, W. D.; Ngueyn, H. T. Plant Biotech. J. 2011, 1-8.
- "Molecular Characterization and Functional Analysis of Glycine max Sterol Methyltransferase 2 genes Involved in Plant Membrane Sterol Biosynthesis", Neelakandan, A. K.; Nguyen, H. TM.; Kumar, R.; Tran, L-S.; Guttikonda, S. K.; Quach, T. N; Donovan, A.; Nes, W. D.; Nguyen, H. T. Plant Mole. Biol. 2010, 74, 503-518 .
- "Expression, Purification, and Characterization of Aspergillus fumigatus Sterol 14-alpha Demethylase (CYP51) Isoenzymes A and B", Warrilow A. G; Melo N; Martel C. M; Parker J. E; Nes W. D; Kelly S. L; Kelly D. E. Antimicrob. Agents Chemother 2010, 54, 4225-34.
- "Azole Binding Properties of Candida albicans Sterol 14-alpha-demethylase (CACYP51)", Warrilow, A. G. S.; Martel, C. M.; Parker, J. E.; Melo, N. R.; Lamb, D. C.; Nes, W. D.; Kelly, D. E.; Kelly, S. K. Antimicrobiol. Agents Chemother 2010, 54, 4235-4245.
- "Cloning, Mechanistic and Functional Analysis of a Fungal Sterol 24-C methyltransferase Implicated in Brassicaterol Biosynthesis", Pereira, M.; Song, Z.; Santos-Silva, L. K.; Richards, M. R.; Nguyen, T. T.; Liu, J.; Ganapathy, K.; Nes, W. D. Biochm. Biophys. Acta 2010, 1801, 1163-1174.
- "Crystal Structures of Ligand-free and Inhibitor-Bound Sterol 14a-Demethylase from Trypansoma brucei", Lepesheva, G. I.; Park, H-W.; Hargrove, T. Y.; Vanhollebeke, B.; Zdzislaw, W.; Harp, J. M.; Sundaramoorthy, M.; Nes, W. D.; Pays, E.; Villalta, F.; Waterman, M. R. 99. J. Biol. Chem. 2010, 285, 1773-1780. [cover page]
- "Sterol Methyltransferase: Functional Analysis of Highly Conserved Residues by Site-directed Mutagenesis", Nes, W.D.; Jayasimha, P.; Zhou, W.; Kanagasabai, R.; Jin, C.; Jaradat, T.T.; Shaw, R.W.; Bujnicki, J.M. Biochemistry 2004, 43, 569-576.
- "Biosynthesis of Phytosterols: Kinetic Mechanism for the Enzymatic C-methylation of Sterols", Nes, W.D.; Song, Z.; Dennis, A.L.; Zhou, W.; Nam, J.; Miller, M.B. J. Biol. Chem. 2003, 278, 34505-34516.
- "Enzyme Mechanisms for Sterol C-methylations", Nes, W.D. Phytochemistry 2003, 64, 75-95.
- "Purification, Characterization and Catalytic Properties of Human Sterol 8-isomerase", Nes, W.D.; Zhou, W.; Dennis, A.L.; Li, H.; Jia, Z.; Keith, R.A.; Piser, T.M.; Furlong, S.T. Biochem. J. 2002, 367, 587-599.
- "Active Site Papping and Substrate Channeling in the Sterol Methyltransferase Pathway", Nes, W.D.; Marshall, J.A.; Jia, Z.; Jaradat, T.T.; Song, Z.; Jayasimha, P. J. Biol. Chem. 2002, 277, 42549-42556.