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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
     

Education
Graduate  Jadavpur University    1989  PhD 


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

Graduate Biomedical Sciences Affiliations
Biochemistry and Molecular Genetics Program 
Biochemistry and Structural Biology 
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 Chagasí disease. The disease affects 16-18 million people and causes 50,000 deaths annually. Despite the enormous global burden of Chagasí 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
Cook WJ, Senkovich O, Aleem K, Chattopadhyay D.

PLoS One. 2012;7(10):e46875. doi: 10.1371/journal.pone.0046875.  
23056503 
Sartmatova D, Nash T, Schormann N, Nuth M, Ricciardi R, Banerjee S, Chattopadhyay D.

Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013 Mar 1;69(Pt 3):295-301 
23519808 
Schormann N, Banerjee S, Ricciardi R, Chattopadhyay D.

Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013 Dec;69(Pt 12):1328-34. 
24316823 
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 
Chattopadhyay, D., Rayner, J., McHenry, A.M., and Adams, J. H. (2006) “The 3D structure of Plasmodium falciparum EBA175 ligand domain provides unexpected insight into the molecular basis of host specificity for malaria parasites” Trends in Parasitology 22, 143-145  16497558 
Chattopadhyay, D., Rayner, J., McHenry, A.M., and Adams, J. H. (2006) “The 3D structure of Plasmodium falciparum EBA175 ligand domain provides unexpected insight into the molecular basis of host specificity for malaria parasites” Trends in Parasitology 22, 143-145  16497558 
Senkovich, O., Bhatia, V., Garg, N. & Chatopadhyay, D. (2005) “Lipophilic Antifolate Trimetrexate is a Potent Inhibitor of Trypanosoma cruzi” Antimicrob. Chemother. Antimicrob. Chemother. 49, 3234-323  16048931 
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 
Costanzo, M. J, Yabur, S. C, Almond Jr., H. R., Andrade-Gordon, P, Corcoran, T. W., de Garavilla, L., Kauffman, J. A., Abraham, W. M., Recacha, R, Chattopadhyay, D. and Maryanoff, B. E. (2003) “Potent, Small-Molecule Inhibitors of Human Mast Cell Tryptase. Antiasthmatic Action of a Dipeptide-Based Transition-State Analogue Containing a Benzothiazole Ketone” J. Med. Chem. 46, 3865-3876  12930148 
Quevillon, E., Spielmann, T., Brahimi, K., Chattopadhyay, D., Yeraman, E. & Langsley, G. (2003) “The Plasmodium falciparum family of RabGTPases.” Gene 306, 13-25  12657463 
Senkovich, O., Pal, B., Schormann, N.S. & Chattopadhyay, D. (2003) “Trypanosoma cruzi genome encodes a pteridine reductase 2 protein.” Mol. Biochem. Parasitol. 127. 89-92  12615341 
Greco, M.N., Hawkins, M.J., Powell, E.T., Almond, H.R., Corcoran, T.W., Garavilla,L., Kauffman, J.A., Recacha, R., Chattopadhyay, D., Andrade-Gordon, P. & Maryanoff, B.E. (2002) “Nonpeptide inhibitors of Cathepsin G: optimization of a novel b-ketophosphonic acid lead by structure-based drug design”. J. Am. Chem. Soc. 124, 3810-3811.  11942800 
Recacha, R., Costanzo, M.J., Maryanoff, B. & Chattopadhyay, D. (2002) “Crystal Structure of Human Carbonic Anhydrase II Complexed with an Anticonvulsant Sugar Sulfamate.” Biochem. J. 361, 437-441.  11802772 
Chattopadhyay, D., Langsley, G., Carson, M., Recacha, R., DeLucas, L.J. & Smith, C. D. (2000) “Crystal structure of the Nucleotide Binding Domain of Plasmodium falciparum Rab6 GTPase in the GDP Bound Form”. Acta Cryst D. Biol. Crystallography 56, 937-944  10944329 
Costanzo, M. J, Yabur, S. C, Almond Jr., H. R., Andrade-Gordon, P, Corcoran, T. W., de Garavilla, L., Kauffman, J. A., Abraham, W. M., Recacha, R, Chattopadhyay, D. and Maryanoff, B. E. (2003) “Potent, Small-Molecule Inhibitors of Human Mast Cell Tryptase. Antiasthmatic Action of a Dipeptide-Based Transition-State Analogue Containing a Benzothiazole Ketone” J. Med. Chem. 46, 3865-3876  12930148 
Schormann, N., Senkovich, O., Ananthan, S. & Chattopadhyay, D. (2003) “Docking and Biological Activity of Pteridine Analogs: Search for Inhibotors of Pteridine Reductase Enzymes from Trypanosoma cruzi.” THEOCHEM 635, 37-44   

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