Professor of Chemistry
Professor of Molecular Biophysics and Biochemistry
Member of Yale faculty since 2001
Research Flexibility is an integral part of enzyme function. This conformational motion can include reorganization of catalytic groups, loop closures, and domain movements, to name a few. In enzymes these motions are often the rate-determining step in the catalytic process. Their characterization is therefore crucial to understanding enzyme function, for optimizing catalysts, for understanding protein-ligand interactions, and for de novo enzyme design. The focus of our research is to understand how the dynamic and structural properties of proteins correlate with their function with particular emphasis on enzymes and allosterism.
Our primary experimental tool for addressing these questions is solution nuclear magnetic resonance (NMR) spectroscopy, which allows quantitative, atomic-resolution insight into the kinetics, thermodynamics, and mechanism these important enzyme motions.
B.S. George Washington University, 1990
Ph.D. University of Notre Dame, 1997
NIH Postdoctoral Fellow-Columbia University, 1997-2001
Camille and Henry Dreyfus New Faculty award, 2001
NSF CAREER Award, 2003
Alfred P. Sloan Fellow, 2004
I. Rivalta, M.M. Sultan, N.S. Lee, G. Manley, J.P. Loria, & V. Batista. Allosteric pathways in the imidazole glycerol phosphate synthase. Proc. Natl. Acad. Sci, USA 2012, 109, E1428-E1436.
G. Manley, I. Rivalta, & J.P. Loria. NMR and computation for the study of enzyme allostery. J. Phys. Chem. 2013, B 117, 3063-3073.
S.K. Whittier, A. Hengge, & J.P. Loria. Conformational motions regulate phosphoryl transfer in related protein tyrosine phosphatases. Science 2013, 341, 899-903.
M.A. Frey, Z.M. Sethna, G.A. Manley, S. Sengupta, K.W. Zilm, J.P. Loria, & S.E. Barrett. Accelerating multidimensional NMR and MRI experiments using iterated maps. J. Magn. Reson. 2013, 237, 100-109.
X. Zhai, M.K. Go, A.C. O'Donoghue, T.L. Amyes, S.D. Pegan, Y. Wang, J.P. Loria, A.D. Mesecar, & J.P. Richard. The Effect of Replacement and Deletion Mutations of Loop 6 on Catalysis by Triosephosphate Isomerase. Biochemistry 2014, 53, 3486-3501.