University of Illinois
116 Morrill Hall, Box B-4
505 South Goodwin Avenue
Urbana, IL 61801
Additional Campus Affiliations
Stephen G. Sligar received his Ph.D. in Physics from the University of Illinois in 1975. Dr. Sligar served on the faculty in the Department of Molecular Biophysics and Biochemistry at Yale University and returned to the University of Illinois in 1982 where he was the I. C. Gunsalus Professor of Biochemistry. He now holds the University of Illinois Swanlund Endowed Chair and is Director of the School of Molecular and Cellular Biology. He is also a faculty member in the Department of Chemistry, the Center for Biophysics and Computational Biology and the College of Medicine. Dr. Sligar holds affiliate appointments in the Beckman Institute for Advanced Science and Technology, the Institute for Genomic Biology and The Micro and Nano Technology Laboratory on the Illinois campus. He is a Fellow of the Biophysical Society and the American Association for the Advancement of Science. Awards include a Fulbright Research Scholarship, Senior Fellowship from the Japan Society for the Promotion of Science, an NIH Merit Award and the Bert L. and Kuggie Vallee Visiting Professorship in Inorganic Chemistry at Oxford where he was a Fellow of Queens College. He is also a Fellow in the Jerome Karle Nobel Laureate World Innovation Foundation. Dr. Sligar's research is supported by grants from the National Science Foundation, the National Institutes of Health and the Human Frontiers Program. Research centers on understanding the structure and mechanistic function of metalloenzymes, membrane bound receptors and transporters as well as investigations in blood coagulation and amyloid proteins and their corresponding human disease states.
physical and chemical mechanisms of oxygenase catalysis; self-assembled nanoscale complexes; development of therapeutics for human disease targets
Our research efforts seek a precise understanding of the mechanisms of biological oxidation, the structure of collective assemblies of organized protein, lipid, and nucleic acid systems, the basis of molecular recognition in protein-protein and protein-nucleic acid complexes, and the detailed chemistry and physical operation of oxygenase and oxidase catalysis.
One research focus is on the cytochrome P450-dependent mixed-function oxidases that play central and crucial roles in mammalian, plant, insect, viral, and microbial metabolism. Central questions relating to the mechanisms of these enzymes include the precise chemistry involved in activating oxygen and substrate, and the identity of metal-oxygen-carbon intermediates in the catalytic event, the detailed physical description of inter- and intra-protein electron and proton transfer, and the structure of multi-enzyme membrane complexes involved in catalytic oxygenation and redox movement. We use low-temperature X-ray crystallography as well as cryoenzymology to trap intermediate states. We also are actively pursuing the problems of functional genomics in the large P450 superfamily. Through these efforts we have discovered multiple functions, not only in atmospheric dioxygen metabolism but also via reductive chemistries operating in totally anaerobic environmental niches. We also are investigating protoeomic issues related to thermal and baro-stability and related evolutionary connectivities of human metabolic profiles.
A second focus of our group uses the powerful tools of nanotechnology. As part of the NSF Nanoscale Science and Engineering Center, feedback controlled lithography and dip pen lithograph are being utilized to introduce controlled patterns onto surfaces from the single silicon atom level to the 100 nm scale. We are developing controlled self-assembly processes to generate mesoscale biological assemblies onto these patterned surfaces which can serve as sensors and high throughput screening arrays for pharmaceutical targets. Current efforts introduce single membrane proteins, such as G-protein coupled receptors and human and plant P450 isozymes, into controlled lipid rafts. Readout modalities include surface plasmon resonance, atomic force microscopy and photonic band gap architectures.
B.S. 1970 Drexel University
Ph.D. 1975 University of Illinois, U-C
Postdoc. 1975-76 University of Illinois, U-C
Honors & Awards
Fellow, Biophysical Society
NSF Human Frontiers Science Program Research Award
World Innovation Foundation Fellow
NIH Merit Award
Japan Society for the Promotion of Sciences Senior Fellow
Bert L. and N. Kuggie Vallee Visiting Professor, Oxford University
Denisov, I. G., & Sligar, S. G. (2023). Solvent isotope effects in the catalytic cycle of P450 CYP17A1: Computational modeling of the hydroxylation and lyase reactions. Journal of Inorganic Biochemistry, 243, Article 112202. https://doi.org/10.1016/j.jinorgbio.2023.112202
Miller, J. C., Lee, J. H. Z., Mclean, M. A., Chao, R. R., Stone, I. S. J., Pukala, T. L., Bruning, J. B., De Voss, J. J., Schuler, M. A., Sligar, S. G., & Bell, S. G. (2023). Engineering C-C Bond Cleavage Activity into a P450 Monooxygenase Enzyme. Journal of the American Chemical Society, 145(16), 9207-9222. https://doi.org/10.1021/jacs.3c01456
Shree, S., McLean, M. A., Stephen, A. G., & Sligar, S. G. (2023). Revealing KRas4b topology on the membrane surface. Biochemical and Biophysical Research Communications, 678, 122-127. https://doi.org/10.1016/j.bbrc.2023.08.035
Denisov, I. G., Grinkova, Y. V., McLean, M. A., Camp, T., & Sligar, S. G. (2022). Midazolam as a Probe for Heterotropic Drug-Drug Interactions Mediated by CYP3A4. Biomolecules, 12(6), Article 853. https://doi.org/10.3390/biom12060853
Liu, Y., Denisov, I., Gregory, M., Sligar, S. G., & Kincaid, J. R. (2022). Importance of Asparagine 202 in Manipulating Active Site Structure and Substrate Preference for Human CYP17A1. Biochemistry, 61(7), 583-594. https://doi.org/10.1021/acs.biochem.2c00023