Satish K Nair
Professor of Biochemistry
Professor of Biophysics and Computational Biology
Affiliate, Department of Chemistry
430 Roger Adams Lab
Office: (217) 333-0641
Lab: (217) 333-2688
Fax: (217) 244-5858
Archaea, Biofuels, Drug Discovery, Enzymology, Membrane Biology, Protein Structure, Protein-Nucleic Acid Interactions
B.S. 1989 Brown University
Ph.D. 1994 University of Pennsylvania
Postdoc. 1995-99 Rockefeller University
Natural products biosynthesis, bacterial signalling, X-ray crystallography
Research in the Nair lab focuses on understanding the basis for regulation of bacteria by small molecule natural products. Our laboratory uses classical biochemical and microbiological techniques, in combination with biophysical methods (in particular X-ray crystallography) to decipher how microbes utilize small molecules to establish ecological niches, and combat against the colonization of antagonistic species that may compete for limited resources. This research focus is predicated upon the notion that knowledge of such interactions drives the discovery and development of natural products that can be used to combat the growth of pathogenic bacteria.
Ribosomally synthesized peptide antibiotics: A main research focus in our laboratory is on biosynthetic enzymes that modify ribosomally encoded peptides to yield macrocyclic natural products. We are specifically focused on understanding the mechanism for the synthesis of two classes of such compounds: lantibiotics and cyanobactins. For both classes of natural products, the genetic nature of the precursor and the modular architecture of the modification/processing enzymes may be exploited to yield novel molecules with improved therapeutic applications. Our work on lantibiotics, in collaboration with the van der Donk laboratory (Chemistry: UIUC), has been aimed at characterization of several enzymes involved in biosynthesis. Our work on cyanobactin, in collaboration with Eric Schmidt (Medicinal Chemistry: Utah) focuses on structure-function characterization of enzymatic pathways for the production of these heterocyclized macrocyclic marine natural products.
Phosphonate biosynthesis and engineering: We are members of the Mining Microbial Genomes theme within the Institute of Genomic Biology (van Der Donk: Chemistry, Metcalf: Microbiology and Zhao: Chemical Engineering). In collaboration with the members of this theme, we are focused on characterization of enzymes involved in the biosynthesis of phosphonate antibiotics, with the aim of using the structural data to reprogram these enzymes to produce novel compounds.
Bacterial inter- and intracellular communication: Bacteria can utilize small molecules as signals and we are focusing on elucidating the mechanisms underlying this process. In quorum sensing, bacteria coordinate population growth by utilizing small molecule inducers (typically acylhomoserine lactones). When the population density exceeds some threshold, these autoinducers bind to their cognate receptor and activate the transcription of various genes. A second class of inter-cellular communication is predicated upon the action of a diffusible signal factors that are chemically distinct from quorum sensing autoinducers. These classes of compounds activate the production or degradation of a second messenger, cyclic diguanylate (or cyclic di-GMP) that act as downstream effectors for various signaling pathways. In theory, as each of these pathways are regulated by small molecules, they represent ideal targets for therapeutic intervention against bacterial growth.
- Agarwal, V., Pierce, E., McIntosh, J., Schmidt, E. W., and Nair, S. K. (2012) "Structures of cyanobactin maturation enzymes define a family of transamidating proteases." Chemistry and Biology. 19, 1411-22.
- Agarwal, V., Tikhonov, A., Metlitskaya, A., Severinov, K., and Nair, S. K. (2012) “Structure and Function of a Serine Carboxypeptidase Adapted for Degradation of the Protein Synthesis Antibiotic Microcin C7.” Proc. Nat’l Acad. Sci. USA 109, 4425-30.
- Zou, Y., Zhang, H., Brunzelle, J.S., Johannes, T.W., Woodyer, R., Hung, J.E., Nair, N., van der Donk, W.A., Zhao, H., and Nair, S.K. (2012) “Crystal structures of phosphite dehydrogenase provide insights into nicotinamide cofactor regeneration.” Biochemistry 51, 4263-70.
- Lukk, T., et. al. (2012) “Homology Models Guide Discovery of Diverse Enzyme Specificities among Dipeptide Epimerases in the Enolase Superfamily.” Proc. Nat’l Acad. Sci. USA 109, 4122-27.
- Gonzalez-Gutierrez, G., Lukk, T., Agarwal, V., Papke, D., Nair, S.K., and Grosman, C. (2012) “Mutations that stabilize the open state of the Erwinia chrisanthemi ligand-gated ion channel fail to change the conformation of the pore domain in crystals.” Proc. Nat’l Acad. Sci. USA 109, 6331-36.
- Yoshida, S., Park, D. S., Bae, B., Mackie, R., Cann, I. K., Nair, S. K. (2011) “Structural and Functional Analyses of a Glycoside Hydrolase Family 5 Enzyme with an Unexpected β-Fucosidase Activity.” Biochemistry. 50, 3369-75.
- Agarwal, V., Metlytskaya, A., Severinov, K., and Nair, S. K. (2011) “Structural Basis for Microcin C7 Inactivation by the MccE Acetyltransferase J. Biol. Chem. 286, 21295-303.
- McIntosh, J., Donia, M., Nair, S. K., and Schmidt, E. (2011) “Enzymatic Basis of Ribosomal Peptide Prenylation in Cyanobacteria.” J. Am. Chem. Soc. 133, 13698-705. [Highlighted in Chemical & Engineering News].
- Cobb, R., Bae, B., Zhao, H., and Nair, S. K. (2011) “A New Acetyltransferase Fold in the Structure and Mechanism of the Phosphonate Biosynthetic Enzyme FrbF.” J. Biol. Chem. 286, 36132-41
- Nair, S. K., and Severinov, K. (2011) “Microcin C7: Mechanism of Action and Bacterial Resistance.” Future Microbiology. 7, 281-9
- Agarwal, V., Borisova, S. A., Metcalf, W. W., van der Donk, W. A., and Nair, S. K. (2011) “Structural and Mechanistic Insights into C-P Bond Hydrolysis by Phosphonoacetate Hydrolase.” Chemistry and Biology. 18, 1230-40