Prof. Wolfgang Peti from University of Arizona will give a seminar entitled “Using NMR Spectroscopy to Unravel Enzyme Function” on Friday Sept. 29 at 3:10pm in 1352 Gilman Hall.
The focus of Dr. Peti’s research group is to understand the molecular mechanisms that regulates signalling enzymes. His group combines the information derived from biomolecular NMR spectroscopy, X-ray crystallography, and additional biophysical techniques, such as ITC, DSC, Biacore, and CD spectroscopy.
Dr. Peti has produced almost 100 publications, is an Associate Editor of several biochemistry and biophysics journals, and is a permanent member of the American Diabetes Association's Research Grant Review Committee and of the NIH/MIST study section.
Protein function originates from a cooperation of structural rigidity, dynamics at different timescales and allostery. However, how these three pillars of protein function are integrated is still only poorly understood. Here we show how these pillars are connected in phosphorylation enzymes, specifically the protein tyrosine phosphatase PTP1B and the serine/threonine kinase p38. A broad array of molecular tools are necessary to unravel these function, but NMR plays the key role in analyzing the dynamics that drive the enzymatic cycle as well as allostery that controls enzymatic activity.
1. Protein Phophatase Regulation: The coordinated and reciprocal action of serine/threonine protein kinases and protein phosphatases is a fundamental regulation mechanism for many biological processes. The most biochemically well-characterized protein phosphatase is Protein Phosphatase 1 (PP1), which functions to regulate a variety of cellular processes, from cell cycle progression to neuronal signaling. The ability of PP1 to regulate this broad range of functions is tightly controlled by its interaction with more than 100 different PP1 inhibitory and targeting proteins. Additional projects aim to understand the regulation and substrate specificity of PP3, as well as tyr-phosphatases. As a large number of phosphatase regulatory proteins belong to the family of intrinsically disordered proteins (IDPs) we are also using this model system to understand IDPs mode of action. Our laboratory aims to understand the specificity of these interactions by studying the dynamics and solving the high resolution structures of PP1-regulator proteins both alone and when bound to PP1. By understanding the specificity we will have the possibility to design molecular switches which have the potential to revolutionize treatments for diseases such as Parkinson's disease, diabetes and cancer.
2. Regulation of MAP Kinases: The laboratory is greatly interested understanding the regulation of MAP Kinases. Thus we use a variety of techniques, including NMR spectroscopy and small angle X-ray scattering (SAXS) to determine structural and dynamics to understand MAPK regulation.
3. Inhibition and Regulation of Biofilms: By using E. coli as a model system we are using an integrated approach to understand the underlying
biology of Biofilms. Our laboratory is mainly involved in the structure determination of key proteins for Biofilm formation. Solving the structure of these proteins will enable us to understand their function in the formation of Biofilms. About 85% of human bacterial infections involve biofilms so understanding the genetic basis of biofilm formation and finding effective ways to prevent biofilms will help to create novel antibiotic drugs.