Biosynthesis of Galactofuranose in Kinetoplastids Novel Therapeutic Targets for Treating Leishmaniasis and Chagas Disease英文文献资料.docVIP

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Biosynthesis of Galactofuranose in Kinetoplastids Novel Therapeutic Targets for Treating Leishmaniasis and Chagas Disease英文文献资料.doc

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Biosynthesis of Galactofuranose in Kinetoplastids Novel Therapeutic Targets for Treating Leishmaniasis and Chagas Disease英文文献资料

SAGE-HindawiAccesstoResearch EnzymeResearch Volume2011,ArticleID415976,13pages doi:10.4061/2011/415976 ReviewArticle BiosynthesisofGalactofuranoseinKinetoplastids: NovelTherapeuticTargetsforTreatingLeishmaniasisand Chagas’Disease MichelleOppenheimer, 1AnaL.Valenciano,1,2andPabloSobrado 1,2 1 2 DepartmentofBiochemistry,VirginiaTech,Blacksburg,VA24061,USA InstitutoTecnol′ogicodeCostaRica,Cartago,CostaRica CorrespondenceshouldbeaddressedtoPabloSobrado,psobrado@ Received15December2010;Revised2March2011;Accepted14March2011 AcademicEditor:ArielM.Silber Copyright?2011MichelleOppenheimeretal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttribution License,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperly cited. Cellsurfaceproteinsofparasitesplayaroleinpathogenesisbymodulatingmammaliancellrecognitionandcelladhesionduring infection. β-Galactofuranose(Galf)isanimportantcomponentofglycoproteinsandglycolipids foundonthecellsurfaceof Leishmaniaspp.andTrypanosomacruzi.β-Galf-containingglycanshavebeenshowntobeimportantinparasite-cellinteraction and protection against oxidative stress. Here, we discuss the role of β-Galf in pathogenesis and recent studies on the Galf- biosynthetic enzymes: UDP-galactose 4 epimerase (GalE), UDP-galactopyranose mutase (UGM), and UDP-galactofuranosyl transferase(GalfT).ThecentralroleinGalf formation,itsuniquechemicalmechanism,andtheabsenceofahomologousenzyme inhumansidentifyUGMasthemostattractivedrugtargetintheβ-Galf-biosyntheticpathwayinprotozoanparasites. 1.Galactofuranose highlighting the importance for Galf in bacteria [13]. Studies have also been conducted to identify inhibitors for M. tuberculosis UGM [14–17]. These studies showed that speci?c inhibitors of M. tuberculosis UGM were able topreventmycobacteriumgrowthand,therefore,validated Galf biosynthesis as a drug target against mycobacteria [14]. β-Galf has also been shown to be present in fungi [18–21]. In the human p