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Engin Serpersu

Professor

UT


Research

Studies of the conformations of substrates and exzymes to determine the catalytic significance of the enzyme-substrate complexes at a mechanistic and structural level is the major area of study in our laboratory. Our work is focused on the understanding of enzymatic catalysis at the molecular and structural level by using NMR, computer modeling, and other biochemical/biophysical techniques combined with the site specific mutations of the enzymes to aid in studies of rational drug design.

Our main work involves mechanistic and structural studies with enzymes that modify antibiotics and render them useless against infectious diseases. We have several such enzymes that modify aminoglycoside antibiotics in different manner. Our goals are to investigate structural and functional basis of substrate promiscuity of these enzymes at a molecular level and bring site/residue-specific interpretation to the global thermodynamic properties of enzyme-antibiotic complexes.

We use NMR as the structural tool and Isothermal Titration Calorimetry (ITC), Electron Paramagnetic resonance (EPR) and other spectroscopic techniques to study kinetic, thermodynamic and dynamic aspects of enzyme-antibiotic complexes. Dat obtained from these structural, kinetic, and thermodynamic studies are then used to design molecules that may mimic antibiotic binding to these enzymes and overcome antibiotic resistance by inhibiting these enzymes that confer resistance in infectious bacteria.

The driving force for our studies is that that are more than fifty known enzymes that modify aminoglycoside antibiotics today and studying a single enzyme in detail is not sufficient to understand interactions of aminoglycosides with enzymes. Our goal is to understand the general principles of antibiotic-enzyme interactions and understand reasons behind the subtrate promiscuity and overlap among these enzymes. Therefore, we use aminoglycoside-modifying enzymes in our studies and determine similarities and differences between the interactions of the enzymes with different aminoglycosides to develop general strategies in the design of drugs to affect all of the aminoglycoside-resistance conferring enzymes.

In addition, owing to the NMR expertise of our Laboratory, we have numerous collaborative studies with researchers from different institutions involving reaction intermediates, peptide structures, and hormones.


Publications

Wright, E. and Serpersu, E. H. (2011) Effects of Proton Linkage on Thermodynamic Properties of Enzyme–Antibiotic Complexes of the Aminoglycoside Nucleotidyltransferase(2?)-Ia. J. Thermodyn. and Catal. “in press”.

Wieninger, S. A, Serpersu, E. H. and Ullmann, G. M. (2011) ATP Binding Enables Broad Antibiotic Selectivity of Aminoglycoside Phosphotransferase(3')-IIIa– An Elastic Network Analysis. J. Mol. Biol.409,450-465.

Serpersu, E. H., Özen, C., Norris, A. L. Steren, C. and Whittemore, N. (2010) Backbone Resonance Assignments of a Promiscuous Aminoglycoside Antibiotic Resistance Enzyme; the Aminoglycoside Phosphotransferase(3')-IIIa. Biomol. NMR Assign. 4, 9-12.

Norris, A. L. and Serpersu, E. H. (2010) Coenzyme A Interactions with the Aminoglycoside Acetyltransferase (3)-IIIb and the Thermodynamics of a Ternary System. Biochemistry 49,4036–4042.

Norris, A. L., Özen, C., and Serpersu, E. H. (2010) Thermodynamics and Kinetics of Antibiotic Association with the Aminoglycoside Acetyltransferase (3)-IIIb: A Resistance Causing Enzyme. Biochemistry 49, 4027-4035.

Norris, A. L. and Serpersu, E. H. (2010) Coenzyme A Interactions with the Aminoglycoside Acetyltransferase (3)-IIIb and the Thermodynamics of a Ternary System. Biochemistry 49, 4036–4042.

Norris, A. D. 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, 8587-8594.

Wu, Lingzhi and Serpersu, E. H. (2009) Deciphering Interactions of the Aminoglycoside Phosphotransferase(3')-IIIa with its Ligands. Biopolymers 91, 801-809.


Contact Information

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