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dc.contributor.authorDamerow, Sebastian
dc.contributor.authorLamerz, Anne-Christin
dc.contributor.authorHaselhorst, Thomas
dc.contributor.authorFuehring, Jana
dc.contributor.authorZarnovican, Patricia
dc.contributor.authorvon Itzstein, Mark
dc.contributor.authorRoutier, Francoise H
dc.date.accessioned2017-05-03T11:47:36Z
dc.date.available2017-05-03T11:47:36Z
dc.date.issued2010
dc.date.modified2011-03-10T08:10:03Z
dc.identifier.issn1083-351X
dc.identifier.doi10.1074/jbc.M109.067223
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.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoen_AU
dc.publisherAmerican Society for Biochemistry and Molecular Biology
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom878
dc.relation.ispartofpageto887
dc.relation.ispartofissue2
dc.relation.ispartofjournalJournal of Biological Chemistry
dc.relation.ispartofvolume285
dc.rights.retentionY
dc.subject.fieldofresearchMedicinal and Biomolecular Chemistry not elsewhere classified
dc.subject.fieldofresearchBiological Sciences
dc.subject.fieldofresearchMedical and Health Sciences
dc.subject.fieldofresearchChemical Sciences
dc.subject.fieldofresearchcode030499
dc.subject.fieldofresearchcode06
dc.subject.fieldofresearchcode11
dc.subject.fieldofresearchcode03
dc.titleLeishmania UDP-sugar Pyrophosphorylase. The missing link in galactose salvage?
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2010
gro.hasfulltextNo Full Text
gro.griffith.authorvon Itzstein, Mark
gro.griffith.authorHaselhorst, Thomas E.


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