PMID- 24256207
OWN - NLM
STAT- MEDLINE
DCOM- 20150115
LR  - 20211021
IS  - 1557-7716 (Electronic)
IS  - 1523-0864 (Print)
IS  - 1523-0864 (Linking)
VI  - 20
IP  - 18
DP  - 2014 Jun 20
TI  - Protein S-nitrosylation in Plasmodium falciparum.
PG  - 2923-35
LID - 10.1089/ars.2013.5553 [doi]
AB  - AIMS: Due to its life in different hosts and environments, the human malaria 
      parasite Plasmodium falciparum is exposed to oxidative and nitrosative 
      challenges. Nitric oxide (NO) and NO-derived reactive nitrogen species can 
      constitute nitrosative stress and play a major role in NO-related signaling. 
      However, the mode of action of NO and its targets in P. falciparum have hardly 
      been characterized. Protein S-nitrosylation (SNO), a posttranslational 
      modification of protein cysteine thiols, has emerged as a principal mechanism by 
      which NO exerts diverse biological effects. Despite its potential importance, SNO 
      has hardly been studied in human malaria parasites. Using a biotin-switch 
      approach coupled to mass spectrometry, we systemically studied SNO in P. 
      falciparum cell extracts. RESULTS: We identified 319 potential targets of SNO 
      that are widely distributed throughout various cellular pathways. Glycolysis in 
      the parasite was found to be a major target, with glyceraldehyde-3-phosphate 
      dehydrogenase being strongly inhibited by S-nitrosylation of its active site 
      cysteine. Furthermore, we show that P. falciparum thioredoxin 1 (PfTrx1) can be 
      S-nitrosylated at its nonactive site cysteine (Cys43). Mechanistic studies 
      indicate that PfTrx1 possesses both denitrosylating and transnitrosylating 
      activities mediated by its active site cysteines and Cys43, respectively. 
      INNOVATION: This work provides first insights into the S-nitrosoproteome of P. 
      falciparum and suggests that the malaria parasite employs the thioredoxin system 
      to deal with nitrosative challenges. CONCLUSION: Our results indicate that SNO 
      may influence a variety of metabolic processes in P. falciparum and contribute to 
      our understanding of NO-related signaling processes and cytotoxicity in the 
      parasites.
FAU - Wang, Lihui
AU  - Wang L
AD  - 1 Biochemistry and Molecular Biology, Interdisciplinary Research Center, Justus 
      Liebig University , Giessen, Germany .
FAU - Delahunty, Claire
AU  - Delahunty C
FAU - Prieto, Judith Helena
AU  - Prieto JH
FAU - Rahlfs, Stefan
AU  - Rahlfs S
FAU - Jortzik, Esther
AU  - Jortzik E
FAU - Yates, John R 3rd
AU  - Yates JR 3rd
FAU - Becker, Katja
AU  - Becker K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140204
PL  - United States
TA  - Antioxid Redox Signal
JT  - Antioxidants & redox signaling
JID - 100888899
RN  - 0 (Proteins)
RN  - 0 (Reactive Nitrogen Species)
RN  - 0 (S-Nitrosothiols)
RN  - 0 (Sulfhydryl Compounds)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 52500-60-4 (Thioredoxins)
RN  - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases)
RN  - K848JZ4886 (Cysteine)
SB  - IM
MH  - Cysteine/*metabolism
MH  - Glyceraldehyde-3-Phosphate Dehydrogenases/metabolism
MH  - Humans
MH  - Mass Spectrometry
MH  - Nitric Oxide/metabolism
MH  - Plasmodium falciparum/*metabolism
MH  - *Protein Processing, Post-Translational
MH  - Proteins/metabolism
MH  - Proteomics
MH  - Reactive Nitrogen Species/*metabolism
MH  - S-Nitrosothiols/*metabolism
MH  - Sulfhydryl Compounds/metabolism
MH  - Thioredoxins/metabolism
PMC - PMC4039001
EDAT- 2013/11/22 06:00
MHDA- 2015/01/16 06:00
PMCR- 2015/06/20
CRDT- 2013/11/22 06:00
PHST- 2013/11/22 06:00 [entrez]
PHST- 2013/11/22 06:00 [pubmed]
PHST- 2015/01/16 06:00 [medline]
PHST- 2015/06/20 00:00 [pmc-release]
AID - 10.1089/ars.2013.5553 [pii]
AID - 10.1089/ars.2013.5553 [doi]
PST - ppublish
SO  - Antioxid Redox Signal. 2014 Jun 20;20(18):2923-35. doi: 10.1089/ars.2013.5553. 
      Epub 2014 Feb 4.