SDS-PAGE analysis of BHMT purification. BHMT samples after each purification step were treated with SDS-PAGE sample buffer and loaded (0.2 ml) onto a Pharmacia PHAST homogeneous 20% gel and then silver stained.

Dr. Momany's research is focused on the generation of atomic structures and the application of these atomic structures to pharmaceutical problems. The research program is multidisciplinary in approach and bridges the fields of molecular biology, biochemistry, pharmacogenomics, and structure-based drug discovery centered on macromolecular X-ray crystallography.

Dr. Momany is developing new methods of crystallizing macromolecules using self-assembing matrices coupled with Phage display technology for high-throughput crystallizations. This technology includes using bacterially produced antibody lattices and small proteins with enhanced symmetry features. Ultimately, the technology is targeted for crystallizing pharmacologically important drug metabolism proteins such as Cytochrome P450 monooxygenases as part of a structural pharmacogenomics program.

Projects encompass four significantly overlaping research areas. First, we have collaborative projects focused on drug discovery targeting the human immunodeficiency virus. We have performed considerable purification and crystallization trials on HIV reverse transcriptase and the HIV p24 proteins. The goal is to obtain diffraction quality crystals of protein-drug complexes. The second area of research is on proteins involved in the metabolism of homocysteine in humans, and a more general interest in proteins involved in heart disease. High levels of homocysteine have been correlated with atherosclerosis. The proteins we study break-down homocysteine: cystathionine b-synthase, cystathionine g-lyase, and betaine:homocysteine methyltransferase. Mutations within these proteins have been correlated with a variety of other disease states in humans including inefficient collagen cross-linking, osteoporosis, and mental retardation.

The third area of research is Structural Pharmacogenomics. We are developing computer algorithms designed to predict mutations in genes that could change an individuals response to therapeutics. This program entails correlating pharmacogenomic information with structurally derived data, such as drug accessibility to binding pockets. The last area of research is focused on structural studies of vitamin B6, pyridoxal-5'-phosphate (PLP) dependent enzymes to understand the biochemical mechanism of the cofactor. We have recently solved the atomic structures of diaminopimelate decarboxylase (my own research) and kyneurininase (collaboration with Robbie Phillips, Chemistry). Further, two of the proteins involved in homocysteine metabolism, cystathionine b-synthase, cystathionine g-lyase, are PLP-dependent enzymes.

	download article:		• Expression of Recombinant Human Betaine: Homocysteine S-Methyltransferase for X-Ray Crystallographic Studies and Further Characterization of Interaction with S-Adenosylmethionine

SELECTED PUBLICATIONS

C. Momany, V. Levdikov, L. Blagova and K. Crews. "Crystallization of Diaminopimelate Decarboxylase from Escherichia Coli-a Stereospecific D-Amino Acid Decarboxylase," Acta Crystallographica, 2002, section D.

N. Bose, P. Greenspan and C. Momany. "Expression of Recombinant Human Betaine: Homocysteine S-Methyltransferase for X-ray Crystallographic Studies and Further Characterization of Interaction with S-Adenysylmethionine," Protein Expression and Purification, 2002.

T. Clark, C. Momany and E. Neidle. "The benPK Operon, Proposed to Play a Role in Transport, is Part of the Regulon for Benzoate Catabolism in Acinetobacter sp. Strain ADP1," Microbiology, 2002.

B.D. Shaw, C. Momany and M. Momany. "Aspergillus Nidulans nmtA, an N-myristoyl Transferase, Complements the swoF Polarity Mutant," Eukaryotic Cell, 2002.

K. Lee, W. Zhou, L.C. Kelley, C. Momany, C.K. Chu. "Synthesis of Unsaturated Fluoride Containing D- and L-pyranosyl Nucleosides," Tetrahedron: Asymmetry, 2002.

N. Bose and C. Momany. "Crystallization and Preliminary X-Ray Crystallographic Studies of Recombinant Human Betaine:Homocysteine S-Methyltransferase," ACTA Crystallographica, 2001.

C. Momany, L. Kovari, A. Prongay, W. Keller, R. Gitti, B. Lee, A. Gorbalenya, L. Tong , J. McClure, L. Ehrlich, M. Summers, C. Carter and M.G. Rossmann. "Crystal Structure of Dimeric HIV-1 Capsid Protein," Nature Struct. Biol., 1996.

C. Momany, S. Ernst, N-L Chang, R. Ghosh and M.L. Hackert. "Crystallographic Structure Solution of the Lactobacillus 30A ODC to 3.0 A Resolution," J. Mol. Biol., 1995.

About the Center .::. Mission .::. News from the Center .::. Faculty and Research .::. Facilities .::. Contact the Center .::. Home