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Faculty Detail     Name DEBASISH CHATTOPADHYAY   Campus Address CBSE 250 Zip 4400 Phone 205-934-0124 E-mail debasish@uab.edu Other websites

Faculty Appointment(s) Appointment Type Department Division Rank Primary  Medicine  Med - Infectious Diseases Associate Professor Secondary  Biochemistry & Molecular Genetics  Biochemistry & Molecular Genetics Assistant Professor Secondary  Cell, Developmntl, & Integrative Biology  Cell, Developmntl, & Integrative Biology Associate Professor Secondary  Microbiology  Microbiology Assistant Professor Center  Comprehensive Cancer Center  Comprehensive Cancer Center Associate Professor Center  General Clinical Research Center  Minority Health & Research Center Associate Professor

Graduate Biomedical Sciences Affiliations Biochemistry and Molecular Genetics Program  Cellular and Molecular Biology Program  Integrative Biomedical Sciences

Biographical Sketch  Dr. Debasish Chattopadhyay received his BS in Chemistry and MS in Biochemistry from Calcutta University, India. He obtained Ph.D. degree in Chemistry from Jadavpur University, India in 1989. He conducted his postdoctoral research at the Upjohn Company in Michigan. This work was part of an NIH funded collaborative effort involving several academic institutions and pharmaceutical industries for the discovery of potent antiretroviral drugs. Dr. Chattopadhyay's work focussed on the structure-function analysis of target enzymes its application in drug development. Dr. Chattopadhyay joined the University of Alabama in 1994 and was recruited as an Assistant Professor in the School of Medicine in 1998. Dr. Chattopadhyay was promoted to the Associate Professor rank in 2007.

Research/Clinical Interest Title Structure-Function Analysis of Proteins Description The main objective of our research is to define the relationship between the structure and function of biological macromolecules. Single crystal X-ray diffraction analysis combined with a variety of modern state-of-the-art techniques is used to investigate the structural basis of cellular functions. Research in our laboratory is focused in three main areas: STRUCTURAL BIOLOGY OF PATHOGENIC PARASITES Parasitic diseases pose major public health threat worldwide. Research in our laboratory seeks to improve our understanding of the biochemical and biological processes regulating the life cycle of these parasites with the ultimate goal of identifying exploitable drug targets for developing chemotherapeutic strategy. Currently there are three projects under this program. Folate metabolic pathway of Trypanosoma cruzi. Trypanosoma cruzi is a protozoan parasite which causes Chagas’ disease. The disease affects 16-18 million people and causes 50,000 deaths annually. Despite the enormous global burden of Chagas’ disease, no drug is effective in chronic stage and those used for treatment of acute disease result in toxic side effects. With more than 100 million people in 20 countries at risk, yet no hope for a vaccine in the foreseeable future, there is an urgent need for effective chemotherapy for millions of infected individuals. Drugs targeting folate metabolic enzymes have been remarkably successful in the treatment of infectious diseases including parasitic diseases such as malaria. Our research currently focuses on the application of a three dimensional structure-based approach for designing specific and potent inhibitors of T. cruzi dihydrofolate-thymidylate synthase enzyme. Crystal structures of the bifunctional enzyme in complex with substrates and inhibitor have been determined. We have identified a low nanomolar inhibitor of the enzyme as a potent inhibitor of the T. cruzi parasite. Protein trafficking machinery of Plasmodium falciparum. Soon after infecting the human host the malaria parasite enters the red blood cells where it multiplies and actively modifies the host cells. Most of the pathophysiological conditions of human malaria caused by P. falciparum are associated with this intraerythrocytic stage. Inside the erythrocyte the parasites are surrounded by three layers of membrane: the parasitophorous vacuole membrane (PVM), the parasites own plasma membrane and the red blood cells own membrane. Yet the parasite encoded proteins are able to transport from inside the parasite all the way to the outer surface of red blood cells. Proteins displayed on the surface of red blood cells are strategically important for the survival of the parasite and of great significance to the disease outcome. Understanding the mechanism of protein trafficking by P. falciparum is therefore of great interest. Our laboratory focuses on the vesicle mediated trafficking machinery of P. falciparum. STRUCTURE OF BACTERIAL SURFACE PROTEINS AND RECEPTORS The goal of this program is to elucidate three dimensional structures of bacterial surface proteins and their receptor complexes. Structural information allows us to understand the interaction of these proteins with their receptors and their role in virulence and pathogenesis. This knowledge can be used for designing vaccines and therapeutic tools. One of the projects in this program aims at defining surface epitopes on the pneumococcal surface protein A of Streptococcus pneumonia which is a major virulence factor and a vaccine candidate and elucidating the molecular basis of its recognition and binding to lactoferrin. In the second project in this program we are studying the three dimensional structure of a major virulence factor, Psn, of Yersinia pestis, the causative agent of bubonic plague. This outer membrane protein is a dual receptor for the siderophore, yersiniabactin and for the bacteriocin, pesticin. STRUCTURAL BIOLOGY OF EMERGING PATHOGENS OF BIODEFENSE SIGNIFICANCE In this program we are using the structural information from a number of potential drug targets of small pox virus for designing and developing novel chemotherapeutic agents. The targets currently under investigation are deoxyuridine triphosphatase, uracil DNA glycosylase and thymidine kinase. Availability of high resolution structures of these proteins will aid in design and development of specific inhibitors of this key enzyme.

Selected Publications  Publication PUBMEDID Senkovich, O., Cook, W. J., Mirza, S., Holligshead, S. K., Protasevich, I. I., Briles, D. E. & Chattopadhyay, D. (2007) "Structure of a Complex of Human Lactoferrin N-lobe with Pneumococcal Surface Protein A Provides Insight into Microbial Defense Mechanism". J. MOl. Biol. 370, 701-713.  157543335  Cook, W. J., Senkovich, O. & Chattopadhyay, D. (2011) “Crystal Structure of Plasmodium falciparum ARF GTPase Activating Protein” Acta Cryst. F. Struct Biol Cryst Commn. 67, 1339-1344  22102228  Schormann, N., Sommers, C., Prichard, M., Noah, J., Nuth M., Ricciardi, R.P. & Chattopadhyay, D. (2011) “Identification of protein-protein interaction inhibitors targeting vaccinia virus processivity factor for developing antiviral agents” Antiomicrob. Chemother. 55, 5054-5062   21844323   Smith, C. D., Chattopadhyay, D. & Pal, B. (2011) Crystal structure of Plasmodium falciparum phosphoglycerate kinase: evidence for anion binding in the basic patch. Biochem. Biophys. Res. Commun. 412, 203-206   21798238   Chattopadhyay, D., Corey, A., Dramsi, S., Caliot, E., Layton, J. R., Bohnsack, J. F., Webb, R. I., Adderson, E. & Ulett, G. (2010) “Phylogenetic Lineage and Pilus Protein Spb1/SAN1518 Affect Opsonin-Independent Phagocytosis and Intracellular Survival of Group B Streptococcus” Microbes & Infection. 79, 2070-2078  21238599  Cook, W. J., Senkovich, O., Holder, A. A. & Chattopadhyay, D. (2010) “Structure of Plasmodium falciparum ADP-ribosylation factor” Acta Cryst. F. Struct Biol Cryst Commn. 66, 1426-1431 (cover page).  21045287  Schormann, N., Velu, S., Murugesan, S., Senkovich, O., Walker, K., Chenna, B., Shinkre, B., Desai, A., & Chattopadhyay, D. (2010) “Synthesis and characterization of potent inhibitors of Trypanosoma cruzi dihydrofolate reductase” Bioorg. Med. Chem. 18, 4056-4066  20452776  Schormann N, Senkovich O, Walker K, Wright DL, Anderson AC, Rosowsky A, Ananthan S, Shinkre B, Velu S, Chattopadhyay D. (2008) "Structure-based approach to pharmacophore identification, in silico screening, and three-dimensional quantitative structure-activity relationship studies for inhibitors of Trypanosoma cruzi dihydrofolate reductase function" Proteins 73, 889-901  18536013  Schorann, N., Grigorian, A., Samal, A., Raman, K., DeLucas, L. & Chattopadhyay, D. (2007) "Crystal structure of vaccinia virus uracil-DNA glycosylase reveals dimeric assembly". BMC Struct. Biol. 7, 45   17605817  Prichard, M., Keith, K. A., Johnson M., Harden, E. A., Luo, M., Qiu, S., Chattopadhyay, D. Fan, X., Torrence, P. F. & Kern, E. R. (2007) “Selective Activation of Antiviral Drugs by the Vaccinia Virus Thymidine Kinase” Antimicrob. Agent Chemother. 51, 1795-1803.   17325220  First Prev   1 2 3 of  3  Next Last

Keywords Structural biology, Protein structure function, Malaria, Chagas' disease, Parasitic disease, Small pox, Bacterial pneumoniae

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