Publication:
The impact of nitric oxide toxicity on the evolution of the glutathione transferase superfamily: A proposal for an evolutionary driving force

Issued Date

2013-08-23

Resource Type

Article

ISSN

1083351X
00219258

DOI

10.1074/jbc.M113.476135

Other identifier(s)

2-s2.0-84883184902

Rights

Mahidol University

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SCOPUS

Bibliographic Citation

Journal of Biological Chemistry. Vol.288, No.34 (2013), 24936-24947

Suggested Citation

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 The impact of nitric oxide toxicity on the evolution of the glutathione transferase superfamily: A proposal for an evolutionary driving force. Journal of Biological Chemistry. Vol.288, No.34 (2013), 24936-24947. doi:10.1074/jbc.M113.476135 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/31240

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Title

The impact of nitric oxide toxicity on the evolution of the glutathione transferase superfamily: A proposal for an evolutionary driving force

Author(s)

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

Other Contributor(s)

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

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.

Keyword(s)

Biochemistry, Genetics and Molecular Biology

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https://repository.li.mahidol.ac.th/handle/20.500.14594/31240

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