AIMS: Protein S-glutathionylation is a widely distributed post-translational modification of thiol groups with glutathione that can function as a redox-sensitive switch to mediate redox regulation and signal transduction. The malaria parasite Plasmodium falciparum is exposed to intense oxidative stress and possesses the enzymatic system required to regulate protein S-glutathionylation, but despite its potential importance, protein S-glutathionylation has not yet been studied in malaria parasites. In this work we applied a method based on enzymatic deglutathionylation, affinity purification of biotin-maleimide-tagged proteins, and proteomic analyses to characterize the Plasmodium glutathionylome. RESULTS: We identified 493 targets of protein S-glutathionylation in Plasmodium. Functional profiles revealed that the targets are components of central metabolic pathways, such as nitrogen compound metabolism and protein metabolism. Fifteen identified proteins with important functions in metabolic pathways (thioredoxin reductase, thioredoxin, thioredoxin peroxidase 1, glutathione reductase, glutathione S-transferase, plasmoredoxin, mitochondrial dihydrolipoamide dehydrogenase, glutamate dehydrogenase 1, glyoxalase I and II, ornithine δ-aminotransferase, lactate dehydrogenase, glyceraldehyde 3-phosphate dehydrogenase [GAPDH], pyruvate kinase [PK], and phosphoglycerate mutase) were further analyzed to study their ability to form mixed disulfides with glutathione. We demonstrate that P. falciparum GAPDH, PK, and ornithine δ-aminotransferase are reversibly inhibited by S-glutathionylation. Further, we provide evidence that not only P. falciparum glutaredoxin 1, but also thioredoxin 1 and plasmoredoxin are able to efficiently catalyze protein deglutathionylation. INNOVATION: We used an affinity-purification based proteomic approach to characterize the Plasmodium glutathionylome. CONCLUSION: Our results indicate a wide regulative use of S-glutathionylation in the malaria parasite and contribute to our understanding of redox-regulatory processes in this pathogen.
AIMS: Protein S-glutathionylation is a widely distributed post-translational modification of thiol groups with glutathione that can function as a redox-sensitive switch to mediate redox regulation and signal transduction. The malaria parasitePlasmodium falciparum is exposed to intense oxidative stress and possesses the enzymatic system required to regulate protein S-glutathionylation, but despite its potential importance, protein S-glutathionylation has not yet been studied in malaria parasites. In this work we applied a method based on enzymatic deglutathionylation, affinity purification of biotin-maleimide-tagged proteins, and proteomic analyses to characterize the Plasmodium glutathionylome. RESULTS: We identified 493 targets of protein S-glutathionylation in Plasmodium. Functional profiles revealed that the targets are components of central metabolic pathways, such as nitrogen compound metabolism and protein metabolism. Fifteen identified proteins with important functions in metabolic pathways (thioredoxin reductase, thioredoxin, thioredoxin peroxidase 1, glutathione reductase, glutathione S-transferase, plasmoredoxin, mitochondrial dihydrolipoamide dehydrogenase, glutamate dehydrogenase 1, glyoxalase I and II, ornithine δ-aminotransferase, lactate dehydrogenase, glyceraldehyde 3-phosphate dehydrogenase [GAPDH], pyruvate kinase [PK], and phosphoglycerate mutase) were further analyzed to study their ability to form mixed disulfides with glutathione. We demonstrate that P. falciparum GAPDH, PK, and ornithine δ-aminotransferase are reversibly inhibited by S-glutathionylation. Further, we provide evidence that not only P. falciparum glutaredoxin 1, but also thioredoxin 1 and plasmoredoxin are able to efficiently catalyze protein deglutathionylation. INNOVATION: We used an affinity-purification based proteomic approach to characterize the Plasmodium glutathionylome. CONCLUSION: Our results indicate a wide regulative use of S-glutathionylation in the malaria parasite and contribute to our understanding of redox-regulatory processes in this pathogen.
Authors: Rovshan G Sadygov; Jimmy Eng; Eberhard Durr; Anita Saraf; Hayes McDonald; Michael J MacCoss; John R Yates Journal: J Proteome Res Date: 2002 May-Jun Impact factor: 4.466
Authors: Randen L Patterson; Damian B van Rossum; Adam I Kaplin; Roxanne K Barrow; Solomon H Snyder Journal: Proc Natl Acad Sci U S A Date: 2005-01-26 Impact factor: 11.205
Authors: Niki L Reynaert; Karina Ckless; Amy S Guala; Emiel F M Wouters; Albert van der Vliet; Yvonne M W Janssen-Heininger Journal: Biochim Biophys Acta Date: 2006-02-20
Authors: Ahmed Gaballa; Bui Khanh Chi; Alexandra A Roberts; Dörte Becher; Chris J Hamilton; Haike Antelmann; John D Helmann Journal: Antioxid Redox Signal Date: 2014-03-13 Impact factor: 8.401
Authors: Hanafy M Ismail; Victoria Barton; Matthew Phanchana; Sitthivut Charoensutthivarakul; Michael H L Wong; Janet Hemingway; Giancarlo A Biagini; Paul M O'Neill; Stephen A Ward Journal: Proc Natl Acad Sci U S A Date: 2016-02-08 Impact factor: 11.205
Authors: James Chun Yip Chan; Alex Cheow Khoon Soh; Dorinda Yan Qin Kioh; Jianguo Li; Chandra Verma; Siew Kwan Koh; Roger Wilmer Beuerman; Lei Zhou; Eric Chun Yong Chan Journal: Mol Cell Proteomics Date: 2018-07-13 Impact factor: 5.911