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Cysteine-3 and Cysteine-4 are Essential for the Thioredoxin-like Oxidoreductase and Antioxidant Activities of Plasmodium Falciparum Macrophage Migration. inhibitory factor

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Title Cysteine-3 and Cysteine-4 are Essential for the Thioredoxin-like Oxidoreductase and
Antioxidant Activities of Plasmodium Falciparum Macrophage Migration.
inhibitory factor
 
Creator Alam, Athar
Goyal, Manish
Iqba, Mohd Shameel
Bindu, Samik
Dey, Sumanta
Pal, Chinmay
Maity, Pallab
Manuel , Mascarenhas Nahren
Ghoshal, Nanda
Bandyopadhyay, Uday
 
Subject Drug Development/Diagnostics & Biotechnology
Infectious Diseases and Immunology
 
Description Plasmodium falciparum macrophage migration inhibitory factor (PfMIF) exhibits thioredoxin (Trx)-like
oxidoreductase activity but the active site for this activity and its function have not been evaluated. A
bioinformatics search revealed that the conserved CXXC motif, which is responsible for Trx-like
oxidoreductase activity, is absent from PfMIF. In contrast, the adjacent N-terminal Cys-3 and Cys-4 are
conserved in MIF across species of malarial parasites. Mutation of either vicinal Cys-3 or Cys-4 of PfMIF
abolished the Trx-like activity, whereas the mutation of the remaining Cys-59 or Cys-103 did not affect it.
PfMIF has an antioxidant function. It prevents reactive oxygen species-mediated lipid peroxidation and
oxidative damage of DNA as evident from DNA nicking assay. Interestingly, chemical modification of the
vicinal cysteines by phenylarsine oxide (PAO), a specific vicinal thiol modifier, significantly prevented this
antioxidant activity. Modification of Cys-3 and Cys-4 was confirmed by MALDI-TOF mass spectroscopy of
peptide fragments obtained after cyanogen bromide digestion of PAO-modified PfMIF. Furthermore, mutation
of either Cys-3 or Cys-4 of PfMIF resulted in the loss of both Trx-like oxidoreductase and antioxidant activities
of PfMIF. Altogether, our results suggest that the vicinal Cys-3 and Cys-4 play a critical role in the Trx-like
oxidoreductase activity and antioxidant property of PfMIF.
 
Publisher Elsevier
 
Date 2011
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1262/1/FREE_RADICAL_BIOLOGY_AND_MEDICINE__50_(11)_1659%2D1668;2011[85].pdf
Alam, Athar and Goyal, Manish and Iqba, Mohd Shameel and Bindu, Samik and Dey, Sumanta and Pal, Chinmay and Maity, Pallab and Manuel , Mascarenhas Nahren and Ghoshal, Nanda and Bandyopadhyay, Uday (2011) Cysteine-3 and Cysteine-4 are Essential for the Thioredoxin-like Oxidoreductase and Antioxidant Activities of Plasmodium Falciparum Macrophage Migration. inhibitory factor. Free Radical Biology & Medicine, 50 (11). pp. 1659-1668.
 
Relation http://dx.doi.org/10.1016/j.freeradbiomed.2011.03.012
http://www.eprints.iicb.res.in/1262/