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dc.contributor.authorDamerow, Sebastianen_US
dc.contributor.authorLamerz, Anne-Christinen_US
dc.contributor.authorHaselhorst, Thomasen_US
dc.contributor.authorFühring, Janaen_US
dc.contributor.authorZarnovican, Patriciaen_US
dc.contributor.authorvon Itzstein, Marken_US
dc.contributor.authorH. Routier, Françoiseen_US
dc.date.accessioned2017-04-24T08:43:13Z
dc.date.available2017-04-24T08:43:13Z
dc.date.issued2010en_US
dc.date.modified2011-03-10T08:10:03Z
dc.identifier.issn00219258en_US
dc.identifier.doi10.1074/jbc.M109.067223en_AU
dc.identifier.urihttp://hdl.handle.net/10072/36881
dc.description.abstractThe Leishmania parasite glycocalyx is rich in galactose-containing glycoconjugates that are synthesized by specific glycosyltransferases that use UDP-galactose as a glycosyl donor. UDP-galactose biosynthesis is thought to be predominantly a de novo process involving epimerization of the abundant nucleotide sugar UDP-glucose by the UDP-glucose 4-epimerase, although galactose salvage from the environment has been demonstrated for Leishmania major. Here, we present the characterization of an L. major UDP-sugar pyrophosphorylase able to reversibly activate galactose 1-phosphate into UDP-galactose thus proving the existence of the Isselbacher salvage pathway in this parasite. The ordered bisubstrate mechanism and high affinity of the enzyme for UTP seem to favor the synthesis of nucleotide sugar rather than their pyrophosphorolysis. Although L. major UDP-sugar pyrophosphorylase preferentially activates galactose 1-phosphate and glucose 1-phosphate, the enzyme is able to act on a variety of hexose 1-phosphates as well as pentose 1-phosphates but not hexosamine 1-phosphates and hence presents a broad in vitro specificity. The newly identified enzyme exhibits a low but significant homology with UDP-glucose pyrophosphorylases and conserved in particular is the pyrophosphorylase consensus sequence and residues involved in nucleotide and phosphate binding. Saturation transfer difference NMR spectroscopy experiments confirm the importance of these moieties for substrate binding. The described leishmanial enzyme is closely related to plant UDP-sugar pyrophosphorylases and presents a similar substrate specificity suggesting their common origin.en_US
dc.description.peerreviewedYesen_US
dc.description.publicationstatusYesen_AU
dc.languageEnglishen_US
dc.language.isoen_AU
dc.publisherAmerican Society for Biochemistry and Molecular Biologyen_US
dc.publisher.placeUnited Statesen_US
dc.relation.ispartofstudentpublicationNen_AU
dc.relation.ispartofpagefrom878en_US
dc.relation.ispartofpageto887en_US
dc.relation.ispartofissue2en_US
dc.relation.ispartofjournalJournal of Biological Chemistryen_US
dc.relation.ispartofvolume285en_US
dc.rights.retentionYen_AU
dc.subject.fieldofresearchMedicinal and Biomolecular Chemistry not elsewhere classifieden_US
dc.subject.fieldofresearchcode030499en_US
dc.titleLeishmania UDP-sugar Pyrophosphorylase. The missing link in galactose salvage?en_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.date.issued2010
gro.hasfulltextNo Full Text


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