Our laboratory uses a combination of X-ray crystallography, bioinformatics, biophysical and biochemical techniques to study the structure and function of proteins. We have greatly benefited from the applications of computational/bioinformatics methods on the whole genome sequence data in the discovery of ’missing links’ in important metabolic pathways. We are particularly interested in enzymes catalyzing key steps in the biosynthetic pathways of cofactors NAD, FAD and coenzyme A in divergent organisms. Despite their essential roles for all living organisms, these pathways display remarkable chemical and structural diversity, signifying their complex evolution history, which often involved horizontal gene transfer events and adaptive evolution of new enzymatic properties. Comprehensive structural and biochemical characterizations of these enzymes are essential for understanding their biological functions and for the structure-base design of novel anti-infectious drugs targeting the biosynthesis pathways of these cofactors.
RESEARCH INTERESTS
Structural enzymology
NAD biosynthesis and regulation
Evolution of protein structure and function
FAD biosynthesis enzymes
Structural genomics
RECENT PUBLICATIONS
Yang, K., Eyobo, Y., Brand, L. A., Martynowski, D., Tomchick, D., Strauss E. and Zhang, H., "Crystal Structure of a Type III Pantothenate Kinase: Insight into the Mechanism of an Essential CoA Biosynthetic Enzyme Universally Distributed in Bacteria." J. Bacteriology, 188:5532-5540, 2006
Cheek, S., Ginakski, K., Zhang, H. and Grishin, N.V., "A comprehensive update of the sequence and structure classification of kinases." BMC Struct Biol., 5(1):6, 2005
Zhang, H., "Protein prenyltransferases" Handbook of Metalloproteins, 3:p37-48, 2004
Karthikeyan, S., Zhou, Q., Mseeh, F., Grishin, N. V., Osterman, A. L. and Zhang, H., "Crystal structure of human riboflavin kinase reveals a b barrel fold and a novel active site arch" Structure, 11:265-273, 2003
Zhang, X., Kurnasov, O. V., Karthikeyan, S., Grishin, N.V., Osterman, A. L., "Structural characterization of a human cytosolic NMN/NaMN adenylyltransferase and implication in human NAD biosynthesis." J. Biol. Chem., 278:13503-11, 2003
SIGNIFICANT PUBLICATIONS
Liu, A. and Zhang, H., "Transition metal-catalyzed nonoxidative decarboxylation reactions." Biochemistry, 45:10407-10411, 2006
Zhang, X., Kurnasov, O. V., Karthikeyan, S., Grishin, N.V., Osterman, A. L., and Zhang, H., "Structural characterization of a human cytosolic NMN/NaMN adenylyltransferase and implication in human NAD biosynthesis." J. Biol. Chem., 278:13503-11, 2003
Karthikeyan, S., Zhou, Q., Mseeh, F., Grishin, N. V., Osterman, A. L. and Zhang, H., "Crystal structure of human riboflavin kinase reveals a b barrel fold and a novel active site arch." Structure, 11:265-273, 2003
Zhou, T., Daugherty, M., Grishin, N. V., Osterman, A. L. and Zhang, H., "Structure and Mechanism of Homoserine Kinase: prototype for GHMP kinase superfamily." Structure, 8:1247-1257, 2000
Zhang, H., Seabra, M. and Deisenhofer, J., "Crystal structure of Rab geranylgeranyl transferase at 2.0E resolution." Structure, 8:241-251, 2000
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