Mostra el registre parcial de l'element

dc.contributorUniversitat Ramon Llull. IQS
dc.contributor.authorPlanas, Antoni (Planas Sauter)
dc.contributor.authorBiarnés Fontal, Xevi
dc.contributor.authorRomero, Javier (Romero García)
dc.contributor.authorFrancisco, Carles
dc.date.accessioned2020-12-23T15:16:19Z
dc.date.accessioned2023-07-13T05:43:40Z
dc.date.available2020-12-23T15:16:19Z
dc.date.available2023-07-13T05:43:40Z
dc.date.issued2013-12
dc.identifier.urihttp://hdl.handle.net/20.500.14342/984
dc.description.abstractGlycoglycerolipids are structural components of mycoplasma membranes with a fundamental role in membrane properties and stability. Their biosynthesis is mediated by glycosyltransferases (GT) that catalyze the transfer of glycosyl units from a sugar nucleotide donor to diacylglycerol. The essential function of glycolipid synthases in mycoplasma viability, and the absence of glycoglycerolipids in animal host cells make these GT enzymes a target for drug discovery by designing specific inhibitors. However, rational drug design has been hampered by the lack of structural information for any mycoplasma GT. Most of the annotated GTs in pathogenic mycoplasmas belong to family GT2. We had previously shown that MG517 in Mycoplasma genitalium is a GT-A family GT2 membraneassociated glycolipid synthase. We present here a series of structural models of MG517 obtained by homology modeling following a multiple-template approach. The models have been validated by mutational analysis and refined by long scale molecular dynamics simulations. Based on the models, key structure-function relationships have been identified: The N-terminal GT domain has a GT-A topology that includes a non-conserved variable region involved in acceptor substrate binding. Glu193 is proposed as the catalytic base in the GT mechanism, and Asp40, Tyr126, Tyr169, Ile170 and Tyr218 define the substrates binding site. Mutation Y169F increases the enzyme activity and significantly alters the processivity (or sequential transferase activity) of the enzyme. This is the first structural model of a GT-A glycoglycerolipid synthase and provides preliminary insights into structure and function relationships in this family of enzymes.eng
dc.format.extent14 p.cat
dc.language.isoengcat
dc.publisherPublic Library of Science (PLoS)cat
dc.relation.ispartofPLoS One. Vol.8, n.12 (2013), e81990cat
dc.rightsAttribution 4.0 International
dc.rights© L'autor/a
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceRECERCAT (Dipòsit de la Recerca de Catalunya)
dc.subject.otherDinàmica molecularcat
dc.subject.otherProteïnes--Estructuracat
dc.subject.otherMicoplasmosiscat
dc.subject.otherEnzimscat
dc.subject.otherCristallscat
dc.subject.otherGlucosiltransferasescat
dc.subject.otherSequence alignmentcat
dc.subject.otherMolecular dynamicscat
dc.subject.otherProtein structurecat
dc.subject.otherProtein structure comparisoncat
dc.subject.otherMycoplasmacat
dc.subject.otherEnzyme structurecat
dc.subject.otherCrystal structurecat
dc.subject.otherGlycosyltransferasescat
dc.titleStructure-function features of a mycoplasma glycolipid synthase derived from structural data integration, molecular simulations, and mutational analysiscat
dc.typeinfo:eu-repo/semantics/articlecat
dc.typeinfo:eu-repo/semantics/publishedVersioncat
dc.rights.accessLevelinfo:eu-repo/semantics/openAccess
dc.embargo.termscapcat
dc.subject.udc577
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0081990cat
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO/PN I+D/BFU2010-22209-C02-02cat


Fitxers en aquest element

 

Aquest element apareix en la col·lecció o col·leccions següent(s)

Mostra el registre parcial de l'element

Attribution 4.0 International
Excepte que s'indiqui una altra cosa, la llicència de l'ítem es descriu com http://creativecommons.org/licenses/by/4.0/
Comparteix a TwitterComparteix a LinkedinComparteix a FacebookComparteix a TelegramComparteix a WhatsappImprimeix