Record Details

Protection against peroxynitrite by pseudoperoxidase from Leishmania major

EPrints@IICB

View Archive Info
 
 
Field Value
 
Title Protection against peroxynitrite by pseudoperoxidase from Leishmania major
 
Creator Bose, Moumita
Saha, Rina
SenSantara, Sumit
Mukherjee, Supratim
Roy, Jayasree
Adak, Subrata
 
Subject Structural Biology & Bioinformatics
 
Description Heme proteinssharetheabilitytodetoxifyreactivenitrogenintermediates(NOandperoxynitrite).But,
to date,noheme-containingenzymaticdefenseagainsttoxicreactivenitrogenintermediateshasbeen
discoveredin Leishmania species.Wehavecloned,expressed,andcharacterizedapseudoperoxidase
from Leishmaniamajor (LmPP) thatiscapableofdetoxifyingperoxynitrite(ONOO�). Optical,EPR,and
resonanceRamanspectralstudiesdemonstratethatONOO� can rapidlyconvertthesix-coordinate
ferric low-spintoaferrichigh-spinformatneutralpH.Westernblottingandimmunofluorescence
studieswithanti-LmPPantibodyshowthatthemature enzymeislocatedattheplasmamembraneof
amastigotes andisexpressedeightfoldhigherinamastigotes comparedtopromastigotes.Moreover,to
further investigateitsexactphysiologicalrolein Leishmania, we havecreatedLmPP-knockoutmutantsby
gene replacementin L. major strains. IC50 valuesforexogenouslyaddedH2O2 or 3-morpholinosydnonimine
(SIN1)showthatdeletionofLmPPin L. major renders thecellmoresusceptibletoSIN1.Thenullmutantcells
exhibitamarkeddecreaseinvirulenceoninfectionwith activatedmacrophagesaswellasinoculationinto
BALB/c mice.Collectively,thesedataprovidestrong evidencethatLmPPplaysanimportantroleinthe
enzymaticdefenseagainstONOO� within macrophages.
 
Date 2012
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1666/1/FRBM_2012.pdf
Bose, Moumita and Saha, Rina and SenSantara, Sumit and Mukherjee, Supratim and Roy, Jayasree and Adak, Subrata (2012) Protection against peroxynitrite by pseudoperoxidase from Leishmania major. Free Radical Biology and Medicine, 53. pp. 1819-1828.
 
Relation http://dx.doi.org/10.1016/j.freeradbiomed.2012.08.583
http://www.eprints.iicb.res.in/1666/