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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/31240
Title: The impact of nitric oxide toxicity on the evolution of the glutathione transferase superfamily: A proposal for an evolutionary driving force
Authors: Alessio Bocedi
Raffaele Fabrini
Andrea Farrotti
Lorenzo Stella
Albert J. Ketterman
Jens Z. Pedersen
Nerino Allocati
Peter C.K. Lau
Stephan Grosse
Lindsay D. Eltis
Antonio Ruzzini
Thomas E. Edwards
Laura Morici
Erica Del Grosso
Leonardo Guidoni
Daniele Bovi
Mario Lo Bello
Giorgio Federici
Michael W. Parker
Philip G. Board
Giorgio Ricci
Department of Chemical Sciences and Technologies
Mahidol University
Universita degli Studi di Roma La Sapienza
University of G. d'Annunzio Chieti and Pescara
McGill University
The University of British Columbia
Seattle Structural Genomics Center for Infectious Disease
Emerald BioStructures Inc.
Universita degli Studi dell'Aquila
IRCCS Ospedale Pediatrico Bambino Gesu
St Vincent's Institute
Bio21 Molecular Science and Biotechnology Institute
Australian National University
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 23-Aug-2013
Citation: Journal of Biological Chemistry. Vol.288, No.34 (2013), 24936-24947
Abstract: Background: Why do ancestral GSTs utilize cysteine/serine as catalytic residues, whereas more recently evolved GSTs utilize tyrosine? Results: Only the more recently evolved GSTs display enough affinity to bind and make harmless the toxic DNDGIC (a natural NO carrier). Conclusion: GST evolution could be linked to the defense against NO. Significance: This represents a further piece in the puzzle of evolutive adaptation to NO toxicity. Glutathione transferases (GSTs) are protection enzymes capable of conjugating glutathione (GSH) to toxic compounds. During evolution an important catalytic cysteine residue involved in GSH activation was replaced by serine or, more recently, by tyrosine. The utility of these replacements represents an enigma because they yield no improvements in the affinity toward GSH or in its reactivity. Here we show that these changes better protect the cell from nitric oxide (NO) insults. In fact the dinitrosyl-diglutathionyl-iron complex (DNDGIC), which is formed spontaneously when NO enters the cell, is highly toxic when free in solution but completely harmless when bound to GSTs. By examining 42 different GSTs we discovered that only the more recently evolved Tyr-based GSTs display enough affinity for DNDGIC (KD < 10-9 M) to sequester the complex efficiently. Ser-based GSTs and Cys-based GSTs show affinities 10 2-104 times lower, not sufficient for this purpose. The NO sensitivity of bacteria that express only Cys-based GSTs could be related to the low or null affinity of their GSTs for DNDGIC. GSTs with the highest affinity (Tyr-based GSTs) are also over-represented in the perinuclear region of mammalian cells, possibly for nucleus protection. On the basis of these results we propose that GST evolution in higher organisms could be linked to the defense against NO. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84883184902&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/31240
ISSN: 1083351X
00219258
Appears in Collections:Scopus 2011-2015

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