Bifunctional role of the leishmanial antimonate reductase LmACR2 as a protein tyrosine phosphatase

Molecular and Biochemical Parasitology
Yao ZhouR Mukhopadhyay

Abstract

LmACR2 is the first identified antimonate reductase responsible for the reduction of pentavalent antimony in pentostam to the active trivalent form of the drug in Leishmania. LmACR2 is a homologue of the yeast arsenate reductase Acr2p and Cdc25 phosphatases and has the HC[X]5R phosphatase motif. Purified LmACR2 exhibited phosphatase activity in vitro and was able to dephosphorylate a phosphotyrosine residue from a synthetic peptide. This phosphatase activity was inhibited by classical inhibitors such as orthovanadate. LmACR2-catalyzed phosphatase activity was inhibited by either antimonate or arsenate. Site-directed mutagenesis experiments showed that the H74C[X]5R81 motif was involved in catalysis. This is the first report of a metalloid reductase with a bifunctional role in protein tyrosine phosphatase activity. Leishmania is never exposed to metalloids during its life cycle. It is therefore unlikely that it would evolve an enzyme exclusively for drug activation. We propose that the physiological function of LmACR2 is to dephosphorylate phosphotyrosine residues in leishmanial proteins.

Citations

Jun 17, 2010·Proceedings of the National Academy of Sciences of the United States of America·Weili YangJohn Ohlrogge
Jun 13, 2006·Plant Physiology·Danielle R EllisDavid E Salt
Oct 3, 2006·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Davide BisacchiDomenico Bordo
Nov 28, 2007·BMC Genomics·Rachel BrenchleyLydia Tabernero
Nov 14, 2013·Journal of Environmental Sciences (China)·Wei ZhengRen Zhang
Aug 9, 2008·Journal of Molecular Biology·Rita MukhopadhyayDomenico Bordo
Mar 29, 2007·The New Phytologist·Gui-Lan DuanYong-Guan Zhu
Apr 9, 2010·FEMS Microbiology Reviews·Robert Wysocki, Markus J Tamás
Jul 3, 2010·Molecular and Biochemical Parasitology·Balázs Szöör
Aug 15, 2006·Journal of Molecular Biology·Joris Messens, Simon Silver
Mar 1, 2012·Chemico-biological Interactions·Ronen Zangi, Montserrat Filella
Jun 13, 2017·Environmental Science & Technology·Yong-Guan ZhuAndrew A Meharg
Jan 17, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Parvin Most, Jutta Papenbrock
Jan 10, 2018·Frontiers in Immunology·Didier Soulat, Christian Bogdan
May 11, 2021·Frontiers in Cellular and Infection Microbiology·Anita Leocadio Freitas-MesquitaJosé Roberto Meyer-Fernandes

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