Human monomethylarsonic acid (MMAv) reductase is a member of the glutathione-S-transferase superfamily

R. A. Zakharyan, A. Sampayo-Reyes, S. M. Healy, G. Tsaprailis, P. G. Board, D. C. Liebler, H. V. Aposhian

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167 Scopus citations

Abstract

The drinking of water containing large amounts of inorganic arsenic is a worldwide major public health problem because of arsenic carcinogenicity. Yet an understanding of the specific mechanism(s) of inorganic arsenic toxicity has been elusive. We have now partially purified the rate-limiting enzyme of inorganic arsenic metabolism, human liver MMAv reductase, using ion exchange, molecular exclusion, and hydroxyapatite chromatography. When SDS-βmercaptoethanol-PAGE was performed on the most purified fraction, seven protein bands were obtained. Each band was excised from the gel, sequenced by LC-MS/MS and identified according to the SWISS-PROT and TrEMBL Protein Sequence databases. Human liver MMAv reductase is 100% identical, over 92% of sequence that we analyzed, with the recently discovered human glutathione-S-transferase Omega class hGSTO 1-1. Recombinant human GSTO1-1 had MMAv reductase activity with Km and Vmax values comparable to those of human liver MMAv reductase. The partially purified human liver MMAv reductase had glutathione S-transferase (GST) activity. MMAv reductase activity was competitively inhibited by the GST substrate, 1-chloro 2,4-dinitrobenzene and also by the GST inhibitor, deoxycholate. Western blot analysis of the most purified human liver MMAv reductase showed one band when probed with hGSTO1-1 antiserum. We propose that MMAv reductase and hGSTO 1-1 are identical proteins.

Original languageEnglish (US)
Pages (from-to)1051-1057
Number of pages7
JournalChemical Research in Toxicology
Volume14
Issue number8
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Toxicology

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    Zakharyan, R. A., Sampayo-Reyes, A., Healy, S. M., Tsaprailis, G., Board, P. G., Liebler, D. C., & Aposhian, H. V. (2001). Human monomethylarsonic acid (MMAv) reductase is a member of the glutathione-S-transferase superfamily. Chemical Research in Toxicology, 14(8), 1051-1057. https://doi.org/10.1021/tx010052h