Positions

Overview

  • 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 and to the Professor rank in 2013.
  • Selected Publications

    Academic Article

    Year Title Altmetric
    2019 Mosquito bite-induced controlled human malaria infection with Plasmodium vivax or P. Falciparum generates immune responses to homologous and heterologous preerythrocytic and erythrocytic antigens 2019
    2019 An overview of structure, function, and regulation of pyruvate kinases 2019
    2016 Poxvirus uracil-DNA glycosylase—An unusual member of the family I uracil-DNA glycosylases 2016
    2016 Small molecule inhibition of the ubiquitin-specific protease USP2 accelerates cyclin D1 degradation and leads to cell cycle arrest in colorectal cancer and mantle cell lymphoma models 2016
    2016 Crystal structures of group B streptococcus glyceraldehyde-3-phosphate dehydrogenase: Apo-form, binary and ternary complexes 2016
    2016 Crystal structures and mutagenesis of PPP-family ser/thr protein phosphatases elucidate the selectivity of cantharidin and novel norcantharidin-based inhibitors of PP5C 2016
    2016 Uropathogenic Escherichia coli engages CD14-dependent signaling to enable bladder-macrophage-dependent control of acute urinary tract infection 2016
    2015 Binding of undamaged double stranded DNA to vaccinia virus uracil-DNA Glycosylase 2015
    2015 Biochemical and structural characterization of Cryptosporidium parvum Lactate dehydrogenase 2015
    2014 Uracil-DNA glycosylases - Structural and functional perspectives on an essential family of DNA repair enzymes 2014
    2014 Structure of Streptococcus agalactiae glyceraldehyde-3-phosphate dehydrogenase holoenzyme reveals a novel surface 2014
    2013 Structure of the uracil complex of Vaccinia virus uracil DNA glycosylase 2013
    2013 Crystallization and preliminary X-ray diffraction analysis of three recombinant mutants of Vaccinia virus uracil DNA glycosylase 2013
    2012 Crystal Structure of Cryptosporidium parvum Pyruvate Kinase 2012
    2011 Identification of protein-protein interaction inhibitors targeting vaccinia virus processivity factor for development of antiviral agents 2011
    2011 Structure of the catalytic domain of Plasmodium falciparum ARF GTPase-activating protein (ARFGAP) 2011
    2011 Crystal structure of Plasmodium falciparum phosphoglycerate kinase: Evidence for anion binding in the basic patch 2011
    2011 Identification of inhibitors that block vaccinia virus infection by targeting the DNA synthesis processivity factor D4 2011
    2011 Malaria immunoepidemiology in low transmission: Correlation of infecting genotype and immune response to domains of Plasmodium falciparum merozoite surface protein 3 2011
    2011 Phylogenetic lineage and pilus protein Spb1/SAN1518 affect opsonin-independent phagocytosis and intracellular survival of Group B Streptococcus 2011
    2010 Vaccinia virus D4 mutants defective in processive DNA synthesis retain binding to A20 and DNA 2010
    2010 Structure of Plasmodium falciparum ADP-ribosylation factor 1 2010
    2010 Synthesis and characterization of potent inhibitors of Trypanosoma cruzi dihydrofolate reductase 2010
    2009 Structures of dihydrofolate reductase-thymidylate synthase of trypanosoma cruzi in the folate-free state and in complex with two antifolate drugs, trimetrexate and methotrexate 2009
    2009 An unexpected phosphate binding site in Glyceraldehyde 3-Phosphate Dehydrogenase: Crystal structures of apo, holo and ternary complex of Cryptosporidium parvum enzyme 2009
    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 2008
    2007 Crystal structure of vaccinia virus uracil-DNA glycosylase reveals dimeric assembly 2007
    2007 Structure of a Complex of Human Lactoferrin N-lobe with Pneumococcal Surface Protein A Provides Insight into Microbial Defense Mechanism 2007
    2007 Selective phosphorylation of antiviral drugs by vaccinia virus thymidine kinase 2007
    2007 Structures of vaccinia virus dUTPase and its nucleotide complexes 2007
    2006 The structure of the Plasmodium falciparum EBA175 ligand domain and the molecular basis of host specificity 2006
    2005 Crystal structure of Trypanosoma cruzi pteridine reductase 2 in complex with a substrate and an inhibitor 2005
    2005 Lipophilic antifolate trimetrexate is a potent inhibitor of trypanosoma cruzi: Prospect for chemotherapy of chagas' disease 2005
    2005 Crystallization of three key glycolytic enzymes of the opportunistic pathogen Cryptosporidium parvum 2005
    2004 Biochemical characterization and crystallization of recombinant 3-phosphoglycerate kinase of Plasmodium falciparum 2004
    2004 Plasmodium falciparum ARFGAP: Expression and crystallization of the catalytic domain 2004
    2003 Docking and biological activity of pteridine analogs: Search for inhibitors of pteridine reductase enzymes from Trypanosoma cruzi 2003
    2003 Potent, small-molecule inhibitors of human mast cell tryptase. Antiasthmatic action of a dipeptide-based transition-state analogue containing a benzothiazole ketone 2003
    2003 A structural model for the inhibition of calpain by calpastatin: Crystal structures of the native domain VI of calpain and its complexes with calpastatin peptide and a small molecule inhibitor 2003
    2003 The Plasmodium falciparum family of Rab GTPases 2003
    2003 Trypanosoma cruzi genome encodes a pteridine reductase 2 protein 2003
    2002 Nonpeptide inhibitors of cathepsin G: Optimization of a novel β-ketophosphonic acid lead by structure-based drug design 2002
    2002 Crystal structure of human L-isoaspartyl-O-methyltransferase with S-adenosyl homocysteine at 1.6-Å resolution and modeling of an isoaspartyl-containing peptide at the active site 2002
    2002 Crystal structure of human carbonic anhydrase II complexed with an anti-convulsant sugar sulphamate 2002
    2001 Expression, purification, crystallization and preliminary crystallographic analysis of recombinant pteridine reductase of Trypanosoma cruzi 2001
    2001 Stabilization of active-site loops in NH3-dependent NAD+ synthetase from Bacillus subtilis 2001
    2001 Crystallization and preliminary x-ray diffraction analysis of protein l-isoaspartyl o-methyltransferase from wheat germ 2001
    2000 Structure of human α-thrombin complexed with RWJ-51438 at 1.7 Å: Unusual perturbation of the 60A-60I insertion loop 2000
    2000 Plasmodium falciparum Rab6 GTPase: Expression, purification, crystallization and preliminary crystallographic studies 2000
    2000 Structure of the nucleotide-binding domain of Plasmodium falciparum Rab6 in the GDP-bound form 2000
    2000 Crystal structure of adenosine kinase from Toxoplasma gondii at 1.8 Å resolution 2000
    2000 Toxoplasma gondii adenosine kinase: Expression, purification, characterization, crystallization and preliminary crystallographic analysis 2000
    1999 Expression, purification, crystallization and preliminary x-ray diffraction analysis of uracil phosphoribosyltransferase of Toxoplasma gondii 1999
    1999 Structural study of Escherichia coli NAD synthetase: Overexpression, purification, crystallization, and preliminary crystallographic analysis 1999
    1998 Large-scale preparation of the Δ10 form of staphylokinase by in vitro processing of recombinant staphylokinase with purified human plasminogen 1998
    1997 Crystal structure of calcium bound domain VI of calpain at 1.9 Å resolution and its role in enzyme assembly, regulation, and inhibitor binding 1997
    1997 Crystallization and preliminary cryogenic x-ray diffraction analyses of protein L-isoaspartyl O-methyltransferase from human fetal brain 1997
    1997 Preliminary crystallographic study on a low molecular weight form of bacterial plasminogen activator staphylokinase 1997
    1997 Purification, crystallization and preliminary X-ray diffraction studies of recombinant calcium-binding domain of the small subunit of porcine calpain 1997
    1996 Crystallographic study of the NAD-dependent M Hoc bond rial malic enzyme from the parasitic roundworm ascaris suum 1996
    1992 Immobilized metal affinity chromatography of bacterially expressed proteins engineered to contain an alternating-histidine domain 1992
    1992 Purification and characterization of heterodimeric human immunodeficiency virus type 1 (HIV-1) reverse transcriptase produced by in vitro processing of p66 with recombinant HIV-1 protease 1992
    1992 Resolution of microheterogeneity associated with recombinant HIV-1 heterodimeric reverse transcriptase 1992

    Research Overview

  • Structure-Function Analysis of Proteins - 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.

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

  • Debasish Chattopadhyay