Engin Serpersu, Ph. D.                                     

Professor and Director,

Center of Excellence for Structural Biology

The University of Tennessee

            Studies of  enzyme-substrate complexes from a mechanistic, structural and drug design perspective 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.

            The major project studied in our laboratory  involves mechanistic and structural studies with enzymes that modify antibiotics and render them useless against infectious diseases.  Current work in our laboratory involves studies of three different enzymes that  catalyze different catalytic reactions to modify aminoglycoside antibiotics and render them useless as antibiotics.  Current studies are concentrated on the determination of solution structures of two enzymes by NMR spectroscopy and computer modeling. Determined conformations of bound substrates will then be used as templates for computer modeling and to search data bases for structurally and chemically similar compounds to develop new inhibitors/antibiotics effective against these enzymes. 

 Selected Recent Publications:

Serpersu, E., H.,  DiGiammarino, E. L., Pappu, K. M., Kunnumal, B. (2001) Substrate binding and catalysis by phosphoglycerate kinase. Recent Research Developments in Protein Engineering   “in press”.

Ekman, D. R., DiGiammarino, E. L., Wright, E., Witter, E. D., Serpersu, E. H.  (2001)  Cloning overexpression and purification of aminoglycoside antibiotic nucleotidyl transferase (2")-Ia: Conformational Studies with bound substrates.  Biochemistry 40,7017-7024.

Cox, J. R., Ekman, D. R.,  DiGiammarino, E. L.,  Akal-Strader, A., and  Serpersu, E. H. (2000) Aminoglycoside Antibiotics Bound to Aminoglycoside-Detoxifying Enzymes and RNA Adopt Similar Conformations.  Cell Biochem. & Biophys.  33,297-308.

Serpersu  E. H., Cox, J. R.,  DiGiammarino, E. L., Mohler, M. L.,Ekman,   D. R.,Akal-Strader,  A.  Owston, M. (2000)  Conformations of Antibiotics in  Active Sites of  Aminoglycoside-Detoxifying Enzymes.  Cell Biochem. & Biophys.  33,309-321.

DiGiammarino, E. L., Draker, K., Wright, G. D., and Serpersu, E. H. (1998). Solution Studies of Isepamicin and conformational comparisons between isepamicin and butirosin A when bound to an aminoglycoside 6¢-N-acetyltransferase determined by NMR spectroscopy. Biochemistry 37,3638-3644.

Mohler, L. M., Cox, J.R., Serpersu, E. H. (1998) Aminoglycoside phosphotransferase(3¢)-IIIa (APH(3¢)-IIIa)-bound conformation of the aminoglycoside lividomycin A characterized by NMR. Carbohydr. Lett. 3,17-24.

Cox, J. R., and Serpersu, E. H. (1997) Biologically important conformations of aminoglycoside antibiotics bound to an aminoglycoside 3¢-phosphotransferase as determined by transferred nuclear Overhauser effect spectroscopy. Biochemistry 36,2353-2359.

Pappu, K. M., Kunnumal, B., and Serpersu, E. H. (1997) A new metal binding site for yeast phosphoglycerate kinase as determined by the use of metal-ATP analog. Biophys. J. 72,928-935.

Cox, R. J., McKay, G. A., Wright, G. D., and Serpersu, E. H. (1996) Arrangement of substrates at the active site of an aminoglycoside antibiotic 3¢-phosphotransferase (APH(3¢)-IIIa) as determined by NMR. J. Am. Chem. Soc. 118,1295-1301.