Office : WLS, F331: 865-974-2668
Lab: WLS, D-413, -417: (865-974-4075, -2530)
Ph.D. Medical School, Hacettepe University (Turkey)
The major project studied in our laboratory involves structural and functional studies of enzymes that modify antibiotics and render them useless against infectious diseases. We use several different enzymes that catalyze different chemical modification reactions of aminoglycoside antibiotics with highly variable substrate profiles ranging from high promiscuity with than dozen antibiotics to low promiscuity of limited to three antibiotics. We also use mesophilic to hyperthermophilic variants of these enzymes to understand molecular basis of their ligand promiscuity as well as thermostability. Current studies are concentrated on the determination of thermodynamic properties of various enzyme–antibiotic complexes, role of solvent in enzyme-ligand interactions, and dynamic properties of these enzymes using NMR, EPR spectroscopy, computer modeling, isothermal and differential scanning calorimetry and other biophysical and biochemical techniques. These studies are aimed to understand dynamic and structural features of enzyme–antibiotic complexes and to determine basic principles of macromolecule–ligand interactions.
Home page: http://www.bio.utk.edu/serpersu/
Norris, A.L., Nickels, J. Sokolov, A. P., and Serpersu, E. H. (2014) Protein dynamics are influenced by the order of ligand binding to an antibiotic resistance enzyme. Biochemistry 53,30-38.
Norris, A. L. and Serpersu, E. H. (2013) Ligand promiscuity through the eyes of the Aminoglycoside N3 Acetyltransferase IIa. Prot. Sci. 22, 916-928.
Jing, X., Wright, E., Bible, A. N., Peterson, C. B., Alexandre, G., Bruce, B. D. and Serpersu, E. H.. (2012) Thermodynamic Characterization of a Thermostable Antibiotic Resistance Enzyme, the Aminoglycoside Nucleotidyltransferase (4ʹ). Biochemistry 51, 9147-9155.
Serpersu, E. H. and Norris, A. L. (2012) Effect of protein dynamics and solvent in ligand recognition by promiscuous aminoglycoside-modifying enzymes. Adv. Carbohydr. Chem. Biochem. (Horton, D. ed.) Elsevier, 67, 221-248.
Norris, A. L. and Serpersu, E. H. (2011) Antibiotic Selection by the Promiscuous Aminoglycoside Acetyltransferase-(3)-IIIb is Thermodynamically Achieved Through Control of Solvent Rearrangement. Biochemistry 50,9309-9317.
Norris, A. L. and Serpersu, E. H. (2009) NMR Detected Hydrogen-Deuterium Exchange Reveals Differential Dynamics of Antibiotic and Nucleotide Bound Aminoglycoside Phosphotransferase 3′-IIIa. J. Am. Chem. Soc. 131,8487-8594.