Hiranmoy Bhattacharjee

Chronic exposure to arsenic mainly from drinking water has been linked to cardiovascular, peripheral vascular and cerebrovascular diseases as well as diabetes and cancer. The health effects of environmental arsenic are an important issue of current public health. The ubiquity of arsenic in the environment has also led to the evolution of arsenic detoxification pathways in every organism. Thus, study of the mechanisms of arsenic detoxification in humans and other organisms is of considerable importance.

In the bacterium E. coli an ATP dependent efflux pump coded for by the arsA and arsB genes extrudes arsenic salts from the cytosol thereby lowering the intracellular concentration of the toxic arsenic. ArsA ATPase is stimulated by arsenite and is the catalytic subunit of the pump while ArsB forms the anion conducting pathway. With the advent of genomic sequencing, homologues of the bacterial ArsA ATPase have been found in nearly every organism examined, including humans. While the enzyme is involved in arsenic detoxification in bacteria, the roles of eukaryotic homologues have not been established. We have recently reported the preliminary characterization of a yeast homologue (ARR4) as well as a mouse homologue (Asna1) of the bacterial arsA gene. The current emphasis is to identify the biochemical and physiological roles of these eukaryotic ArsA homologues. Another area of research is to understand the molecular mechanisms of metalloid detoxification in the legume symbiont Sinorhizobium meliloti.

Yang, H.C., Cheng, J., Finan, T.M., Rosen, B.P., and Bhattacharjee, H. A novel pathway for arsenic detoxification in the legume symbiont Sinorhizobium meliloti. J. Bact. (In press).

Jiang, Y., Bhattacharjee, H., Zhou, T., Rosen, B.P., Ambudkar, S.V., and Sauna, Z.E. Nonequivalence of the nucleotide binding domains of the ArsA ATPase. J. Biol. Chem. 280, 9921-9926 (2005).

Gourbal, B., Sonuc, N., Bhattacharjee, H., Legare, D., Sundar, S., Ouellette, M., Rosen, B.P., Mukhopadhyay, R. Drug uptake and modulation of drug resistance in Leishmania by an aquaglyceroporin. J. Biol. Chem. 279, 31010-31017 (2004).

Bhattacharjee, H., Carbrey, J., Rosen, B.P., and Mukhopadhyay R. Drug uptake and pharmacological modulation of drug sensitivity in leukemia by AQP9. Biochem. Biophys. Res. Commun. 322, 836-841 (2004).

Shen, J., Hsu, C.M., Kang, B.K., Rosen, B.P., Bhattacharjee, H. The Saccharomyces cerevisiae Arr4p is involved in metal and heat tolerance. BioMetals, 16, 369-378 (2003).

Bhattacharjee, H., Rosen, B.P. Structure-function analysis of the ArsA ATPase: Contribution of histidine residues. J. Bioenerg. Biomembr. 33:459-468, 2001.

Bhattacharjee, H., Ho, Y., Rosen, B.P. Genomic organization and chromosomal localization of the Asna1 gene, a mouse homologue of a bacterial arsenic-translocating ATPase gene. Gene, 272:291- 299, 2001.

Bhattacharjee, H., Rosen, B.P. Role of conserved histidine residues in metalloactivation of the ArsA ATPase. BioMetals, 13:281-288, 2000.

Bhattacharjee, H., Zhou, T., Li, J., Gatti, D.L., Walmsley, A.R., Rosen, B.P. Structure-function relationships in an anion-translocating ATPase. Biochem. Soc. Trans. 28:520-526, 2000.

Rosen, B.P., Bhattacharjee, H., Zhou, T., Walsmley, A.R. Mechanism of the ArsA ATPase. Biochim. Biophys. Acta, 1461:207-215, 1999.

Kuroda, M., Bhattacharjee, H., Rosen, B. P. Arsenical pumps in prokaryotes and eukaryotes. Methods Enzymol. 292:82-97, 1998.