Sligar Lab	Stephen G. Sligar I.C. Gunsalus Professor Dept of Biochemistry Dept of Chemistry College of Medicine Center for Biophysics and Computational Biology Director, School of Molecular and Cellular Biology

Overview

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 use of nanoscale assemblies and single molecule methods to define the structure-function relationships in inter- and intra- cellular signaling, the basis of molecular recognition in protein-protein and protein-nucleic acid complexes, and the detailed chemistry and physical operation of oxygenase and catalysts, particularly those involved in human drug metabolism and steroid hormone biosynthesis.

A major research focus is the cytochrome P450 dependent mixed function oxidases which play central and crucial roles in human, plant, insect, viral, and microbial metabolism. Central questions relating to the mechanisms of these important enzymes include the precise chemistry involved in activation of oxygen and substrate, 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. X-ray crystallography at low temperatures and the trapping of intermediate states by cryoenzymology are important tools.

A second important research direction for our group is the development and execution of methodologies for determining the structure of biomolecular assemblies in the 5 nm - 500 nm size range. Providing important structural and functional information on specific aggregates of nucleic acids, lipids and proteins which constitute lipoprotein particles, nucleic acid - protein complexes and single membrane protein assemblies are goals of these research efforts. One current focus is molecular signaling including understanding the role of protein oligomerization of G-protein coupled receptors, development of tools to understand live cell migration, the assembly of focal adeshion complexes and the use of engineered semiconductor nanostructures to investigate single molecular behavior of nucleic acids and proteins.

Last updated: 7/12/08