|BS||Kent State University||Kent, Ohio||Chemistry|
|PhD||Johns Hopkins School of Medicine||Baltimore, Md.||Biochemistry|
Our laboratory studies the three-dimensional structures of proteins relevant to human disease. A major focus of the lab is characterizing bacterial enzymes important to the virulence of infections. Bacterial polysaccharides are often critical determinants of infectivity, and therefore the enzymes involved in carbohydrate biosynthesis are excellent targets for antimicrobial agents. One enzyme family of interest to us is the alpha-D-phosphohexomutase family. These enzymes catalyze the production of phosphorylated sugar precursors that are assembled in more complex carbohydrates. Our laboratory has characterized a protein in one sub-group of the family, the enzyme PMM/PGM from P. aeruginosa. We are currently studying other enzymes in the family from important human pathogens, including B. anthracis, S. aureus, and V. cholerae, using X-ray crystallography and bioinformatic methods. We seek to understand the relationships between protein structure, kinetic mechanisms, and sequence relationships in the family, to facilitate the design of clinical inhibitors. In addition, we are characterizing the role of protein dynamics is the mechanism of P. aeruginosa PMM/PGM via NMR techniques, in collaboration with the laboratory of Steven Van Doren.
Identification of an essential active site residue in the a-D-phosphohexomutase superfamily. Yingying Lee, Ritcha Mehra-Chaudhary, Cristina Furdui, and Lesa J. Beamer, published online 4/8/13 in FEBS Journal
Evolutionary conservation of global motions in an enzyme superfamily across varying quaternary structures. Emily K. Luebbering, Jacob Mick, Ranjan Singh, John J. Tanner, Ritcha Mehra-Chaudhary and Lesa J. Beamer, J Mol Biol (2012) 423: 831-46.
A coevolutionary residue network at the site of a functionally important conformational change in a phosphohexomutase enzyme family. Yingying Lee*, Jacob Mick*, Cristina Furdui, and Lesa J. Beamer. PLOS One 7(6): e38114. (2012). (* denotes co-first authors)
Intrinsic Mobility, Phosphoryl Transfer Defect, and Structure of the 463-Residue Reversible Enzyme, Phosphohexomutase. Akella V.S. Sarma, Asokan Anbanandam, Allek Kelm, Yirui Wei, Ritcha Mehra-Chaudhary, Mark V. Berjanskii, Jacob A. Mick, Lesa J. Beamer* and Steven R. Van Doren* (* denotes co-corresponding authors). Biochemistry (2012) 51(3):807-19.
Quaternary structure, conformational variability, and global motions of phosphoglucosamine mutase. Ritcha Mehra-Chaudhary, Jacob Mick, John J. Tanner, and Lesa J. Beamer. FEBS J. (2011) 278 (18): 3298-3307.
Crystal structure of phosphoglucosamine mutase from B. anthracis, an enzyme in the peptidoglycan biosynthetic pathway. Ritcha Mehra-Chaudhary, Jacob Mick and Lesa J. Beamer. J. Bacteriology (2011) 193 (16): 4081-7
Crystal structure of a bacterial phosphoglucomutase, an enzyme involved in the virulence of multiple human pathogens. Ritcha Mehra-Chaudhary, Jacob Mick, John J. Tanner, Michael T. Henzl, and Lesa J. Beamer, PROTEINS: Structure, function, and bioinformatics (2011) 79 (4): 1215-29.
Domain motion and inter-domain hot spots in a multi-domain enzyme Gwo-Yu Chuang, Ritcha Mehra-Chaudhary, Chi-Ho Ngan, Zerbe BS, Dima Kozakov, Sandor Vajda and Lesa J. Beamer, Protein Science (2010) 19: 1662-72.
Andrew M. Schramm, Dale Karr, Ritcha Mehra-Chaudhary, Steven R. Van Doren, Cristina M. Furdui, Lesa J. Beamer (2010) Breaking the covalent connection: Chain connectivity and the catalytic reaction of PMM/PGM. Protein Science, (2010) 19:1235-1242.
Mehra-Chaudhary R., Neace C.E., and Beamer L.J. Crystallization and initial crystallographic analysis of phosphoglucosamine mutase from Bacillus anthracis. Acta Cryst. F65, 733–735 (2009)
Schramm, A.M., Mehra-Chaudhary R., Furdui, C. M., and Beamer, L.J. Backbone flexibility, conformational change, and catalysis in a phosphohexomutase from Pseudomonas aeruginosa. Biochemistry, 47 (35), 9154–9162 (2008).
Regni, C., Shackelford, G.S., and Beamer, L.J. Complexes of the enzyme PMM/PGM with a slow substrate and inhibitor, Acta Cryst. (2006). F62, 722-726
Regni, C.A., Schramm, A.M., and Beamer, L.J. The reaction of phosphohexomutase from P. aeruginosa: Structural insights into a simple processive enzyme, J. Biol. Chem. 281: 15564-15571 (2006).
Lo, S.-C., Li, X., Henzl, M., Beamer, LJ and Hannink M. analysis of the Keap1:Nrf2 interface reveals a novel mechanism for substrate binding to substrate adaptor proteins, EMBO 25: 3605-3617 (2006).
Beamer, L.J., Li, X., Bottoms, C.A., and Hannink, M. Conserved solvent and side chain structural interactions in the 1.35 Å structure of the Kelch domain of Keap1. Acta Cryst. (2005). D61, 1335-1342.
Li, X., Zhang, D., Hannink, M., and Beamer, L.J. Crystal structure of the Kelch domain of Keap1, J. Biol. Chem. 279: 54750-54758 (2004).
Evolutionary trace analysis of the α-D-phosphohexomutase superfamily. Shackelford, G.S., Regni, C.A., and Beamer, L.J. Protein Science 13:2130-2138 (2004).
Regni, C., Naught, L.E., Tipton, P.A., Beamer, L.J. Structural basis of diverse substrate recognition by the enzyme PMM/PGM from P. aeruginosa, Structure 12: 55-63 (2004).
Research areas: Structural biology: X-ray crystallography of medically important proteins.
How to apply:
Electronic submission is encouraged, e-mail to email@example.com
Applicants should send CV and names of two references to:
Dr. Lesa J. Beamer
117 Schweitzer Hall
University of Missouri
Columbia, MO 65211