Ph.D., Cornell University, Ithaca, NY, 1990
Accepting new M.S. students in fall of 2021: Yes
Accepting new Ph.D. students in fall of 2021: Yes
5300 Scott Hall
Dr. Mitra's research involves trace metals in biology.
Trace metals such as zinc, iron and copper are essential for life and act as cofactors in proteins and as signaling systems. However, they are highly toxic in excess. Other trace metals such as cadmium and lead have no known biological functions and are highly toxic. Maintaining optimal intracellular concentrations of easily available essential trace metals while developing resistance to toxic metals is an important biological problem. Metal transporters located in membranes (both uptake and efflux pumps), together with metal chelators and chaperones, are important in metal homeostatic mechanisms. Our research interests are in studying transporters important for zinc, cadmium, lead and other metals. Defects in zinc and copper transporters have been correlated with many diseases, including cancer, neurological diseases and asthma. Our work takes a biochemical and structural approach to study how metal transporters function. Studying metal transporters at a molecular level will lead to a better understanding of the chemistry of metals in biology and will also be useful in analyzing how defects in metal transporters lead to certain disease diseases.
Recent evidence suggests that there is a link between exposure to and accumulations of high levels of trace metals such as cadmium in the body and genetic background, with increased risk of cancers, such as prostate cancer. Our studies seek to establish if high levels of certain trace metals lead to increased risk of cancer in defined populations.
Techniques used in our laboratory include genetic engineering, membrane protein biochemical characterization, steady-state and stopped-flow kinetics, absorbance and fluorescence spectroscopy, metal ion analysis using ICP-MS, binding studies, and protein structure determination, including structure of metal centers in transporters.
• Roberts, C.S., Muralidharan, S., Ni, F., & Mitra, B. (2021) “The structural role of the first four transmembrane helices in ZntA, a P1B-type ATPase from E.coli”, Biochemistry, DOI 10.1021/acs.biochem.0c00770 (https://dx.doi.org/10.1021/acs.biochem.0c00770).
• Patel, K., Ahmed, Z.S., Huang, X., Yang, Q., Ekinci, E., Neslund-Dudas, C.M., Mitra, B., Elnady, F.A., Ahn, Y.H., Yang, H., Liu, J., & Dou, Q.P. (2018) “Discovering proteasomal deubiquitinating enzyme inhibitors for cancer therapy: lessons learned from rational design, nature and old drug reposition”, Future Medicinal Chemistry 10(17), 2087-2108.
• Narayanasami, S., Liu, S., Li, W., Mathews, F.S., Mitra, B., & Kandavelu, P. (2018) "Structure of the monotopic membrane protein (S)-Mandelate Dehydrogenase at 2.2 Å resolution”, Biochimie 154, 45-54.
• Neslund-Dudas, C., McBride, R.B., Kandegedara, A., Rybicki, B.A., Kryvenko, O.N., Chitale, D., Gupta, N., Williamson, S., Rogers, C., Cardon-Colba, C., Rundle, A., Levin, A., Dou, Q.P., & Mitra, B., (2018) “Association between cadmium and androgen receptor protein expression differs in prostate tumors of African-American and European-American men”, J. of Trace Elements in Medicine and Biology 48, 233-238.
• Schmitt, S., Neslund-Dudas, C., Shen, M., Cui, C., Mitra, B., Dou, Q.P. (2016) “Involvement of ALAD-20S Proteasome Complexes in Ubiquitination and Acetylation of Proteasomal α2 Subunit”, Journal of Cellular Biochemistry 117(1), 144-51.
• Neslund-Dudas, C., Levin, A.M., Beebe-Dimmer, J., Bock, C.H., Nock, N.L., Rundle, A., Jankowski, M., Krajenta, R., Dou, Q.P., Mitra, B., Tang, D., Rebbeck, T.R., & Rybicki, B.A., (2014) “Gene-environment interactions between JAZF1 and occupational and household lead exposure in prostate cancer among African American men”, Cancer Causes Control 25, 869-79.
• Neslund-Dudas, C., Levin, A.M., Rundle, A., Beebe-Dimmer, J., Bock, C.H., Nock, N.L., Jankowski, M., Datta, I., Krajenta, R., Dou, Q.P., Mitra, B., Tang, D., & Rybicki, B.A., (2014) “Case-only gene-environment interaction between ALAD tagSNPs and occupational lead exposure in prostate cancer”, The Prostate 74, 637-46.
• Neslund-Dudas, C., Kandegedara, A., Levin, A.M., Beebe-Dimmer, J., Bock, C.H., Dou, Q.P., Rybicki, B.A., & Mitra, B. (2014) “Prostate tissue metal levels and prostate cancer recurrence in smokers", Biological Trace Elements Research 157, 107-112.
• Neslund-Dudas, C., Mitra, B., Kandegedara, A., Chen, D., Schmidt, S., Shen, M., Cui, Q., Rybicki, B.A., & Dou, Q.P. (2012) “Association of metals and proteasome activity in erythrocytes of prostate cancer cases and controls”, Biological Trace Elements Research 149, 5-9.
• Narayanasami, S., Dewanti, A.R., Merli, A., Rossi, G.L., Mitra, B., & Mathews, F.S. (2009) "Structures of the G81A Mutant of the active chimera of (S)-Mandelate Dehydrogenase and its complex with two of its substrates”, Acta Cryst. D Biol. Crystallogr. 65, 543-552.
• Dutta, S.J., Liu, J., Stemmler, A.J., & Mitra, B. (2007) “Conservative and non-conservative mutations of the residues of the CPC motif in ZntA: effect on metal binding and activity”, Biochemistry 46, 3692-3703.
• Dutta, S.J., Liu, J., Hou, Z., & Mitra, B. (2006) “Conserved Asp714 in transmembrane segment 8 of the ZntA subgroup of P1B-type ATPases is a metal-binding residue”, Biochemistry 45, 5923-5931.
• Liu, J., Dutta, S.J., Stemmler, A.J., & Mitra, B. (2006) “Metal-binding affinity of the transmembrane site in ZntA: implications for metal selectivity”, Biochemistry 45, 763-772.
• Dutta, S., Liu, J., & Mitra, B. (2005) “Kinetics of metal binding to the amino-terminal domain of ZntA by monitoring metal-thiolate charge-transfer complexes”, Biochemistry 44, 14268-14274.
• Liu, J., Stemmler, A.J., Fatima, J. & Mitra, B. (2005) “Metal-binding characteristics of the amino-terminal domain of ZntA: Lead binds to different ligands compared to Cadmium and Zinc”, Biochemistry 44, 5159-5167.
• Dewanti, A.R., Xu, Y. & Mitra, B. (2004) "The Role of Glycine 81 in (S)-Mandelate Dehydrogenase from Pseudomonas putida in Substrate Specificity and Oxidase Activity", Biochemistry 43, 10692-10700.
• Dewanti, A.R., Xu, Y. & Mitra, B. (2004) "Esters of mandelic acid as substrates for (S)-mandelate dehydrogenase from Pseudomonas putida: implications for the reaction mechanism”, Biochemistry 43, 1883-1890.
• Sukumar, N., Dewanti, A.R., Mitra, B. & Mathew, S. (2004) "High Resolution Structures of an Oxidized and Reduced Flavoprotein: the Water Switch in a Soluble form of (S)-Mandelate Dehydrogenase", J. Biol. Chem 279, 3749-3757.
• Dewanti, A.R. & Mitra, B. (2003) "A Transient Intermediate in the Reaction Catalyzed by (S)-Mandelate Dehydrogenase from Pseudomonas putida,” Biochemistry 42, 12893-12901.
• Hou, Z. & Mitra, B. (2003) “Characterization of the metal specificity of ZntA from Escherichia coli using the acylphosphate intermediate", J. Biol. Chem. 278, 28455-28461.
• Xu, Y., Dewanti A.R. & Mitra, B. (2002) "The Arginine165/Arginine277 pair in (S)-Mandelate Dehydrogenase from Pseudomonas putida: role in catalysis and substrate binding", Biochemistry 41, 12313-12319.
• Hou, Z, Narindrasorasak, S., Bhushan, B., Sarkar B. & Mitra B. (2001) “Functional analysis of chimeric proteins of the Wilson Cu(I)-transporting ATPase (ATP7B) and ZntA, a Pb(II)/Zn(II)/Cd(II)-translocating ATPase from Escherichia coli”, J. Biol. Chem. 276, 40858-40863.
• Sukumar, N., Xu, Y., Gatti, D.L., Mitra B. & Mathews, F.S. (2001) “Structure of an Active, Soluble Mutant of the Membrane-Associated (S)-Mandelate Dehydrogenase”, Biochemistry 40, 9870-9878.
• Mitra, B. & Sharma, R. (2001) "The cysteine-rich amino-terminal domain of ZntA, a Pb(II)/Cd(II)/Zn(II)-translocating ATPase from Escherichia coli, is not essential for its function", Biochemistry 40, 7694-7699.
• Lehoux, I.E. & Mitra, B. (2000) "The Role of Arginine277 in (S)-Mandelate Dehydrogenase from Pseudomonas putida in Substrate Binding and Transition State Stabilization", Biochemistry 39, 10055-10065.
• Sharma, R., Rensing, C., Rosen, B.P. & Mitra, B. (2000) "The ATP hydrolytic activity of purified ZntA, a Pb(II)/Cd(II)/Zn(II)-translocating ATPase from Escherichia coli", J. Biol. Chem. 275, 3873-3878.
• Rensing, C., Fan, B., Sharma, R., Mitra, B. & Rosen, B.P. (2000) "CopA: an Escherichia coli Cu(I)-translocating P-type ATPase", Proc. Natl. Acad. Sci. 97, 652-656.