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dc.rights.licenseCC0 — Public Domain
dc.contributor.authorMing, Shonoi A.
dc.contributor.authorCottman-Thomas, Ebony
dc.contributor.authorBlack, Natalee C.
dc.contributor.authorChen, Yi
dc.contributor.authorVeeramachineni, Vamsee
dc.contributor.authorPeterson, Dwight C.
dc.contributor.authorChen, Xi
dc.contributor.authorTedaldi, Lauren M.
dc.contributor.authorWagner, Gerd K.
dc.contributor.authorCai, Chao
dc.contributor.authorLinhardt, Robert J.
dc.contributor.authorVann, Willie F.
dc.date2018
dc.date.accessioned2022-06-20T18:06:32Z
dc.date.available2022-06-20T18:06:32Z
dc.date.issued2018-02-01
dc.identifier.citationInteraction of Neisseria meningitidis group X N-acetylglucosamine-1-phosphotransferase with its donor substrate, S. Ming, E. Cottman-Thomas, N. C. Black, Y. Chen, V. Veeramachineni, D. C. Peterson, X. Chen, G. Wagner, C. Cai, R. J. Linhardt, W. F. Vann, Glycobiology, 28, 100–107, 2018.
dc.identifier.issn14602423
dc.identifier.issn9596658
dc.identifier.urihttps://hdl.handle.net/20.500.13015/5019
dc.identifier.urihttps://doi.org/10.1093/glycob/cwx100
dc.descriptionGlycobiology, 28, 100–107
dc.descriptionNote : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
dc.description.abstractNeisseria meningitidis Group X is an emerging cause of bacterial meningitis in Sub-Saharan Africa. The capsular polysaccharide of Group X is a homopolymer of N-acetylglucosamine α(1–4) phosphate and is a vaccine target for prevention of disease associated with this meningococcal serogroup. We have demonstrated previously that the formation of the polymer is catalyzed by a phosphotransferase which transfers N-acetylglucosamine-1-phosphate from UDP-N-acetylglucosamine to the 4-hydroxyl of the N-acetylglucosamine on the nonreducing end of the growing chain. In this study, we use substrate analogs of UDP-GlcNAc to define the enzyme/donor substrate interactions critical for catalysis. Our kinetic analysis of the phosphotransferase reaction is consistent with a sequential mechanism of substrate addition and product release. The use of novel uracil modified analogs designed by Wagner et al. enabled us to assess whether the CsxA-catalyzed reaction is consistent with a donor dependent conformational change. As expected with this model for glycosyltransferases, UDP-GlcNAc analogs with bulky uracil modifications are not substrates but are inhibitors. An analog with a smaller iodo uracil substitution is a substrate and a less potent inhibitor. Moreover, our survey of analogs with modifications on the N-acetylglucosamine residue of the sugar nucleotide donor highlights the importance of substituents at C2 and C4 of the sugar residue. The hydroxyl group at C4 and the structure of the acyl group at C2 are very important for specificity and substrate interactions during the polymerization reaction. While most analogs modified at C2 were inhibitors, acetamido analogs were also substrates suggesting the importance of the carbonyl group.
dc.description.sponsorshipMedical Research Council
dc.languageen_US
dc.language.isoENG
dc.publisherOxford University Press
dc.relation.ispartofThe Linhardt Research Labs Online Collection
dc.relation.ispartofRensselaer Polytechnic Institute, Troy, NY
dc.relation.ispartofGlycobiology
dc.relation.urihttps://harc.rpi.edu/
dc.rightsCC0 1.0 Universal*
dc.rights.urihttp://creativecommons.org/publicdomain/zero/1.0/*
dc.subjectBiology
dc.subjectChemistry and chemical biology
dc.subjectChemical and biological engineering
dc.subjectBiomedical engineering
dc.titleInteraction of Neisseria meningitidis group X N-acetylglucosamine-1-phosphotransferase with its donor substrateen_US
dc.typeArticle
dcterms.accessRightsA full text version is available in DSpace@RPI
dcterms.isPartOfJournal
dcterms.isVersionOfhttps://doi.org/10.1093/glycob/cwx100
dc.rights.holderCC0 ; this work is in the public domain in the United States.
dc.creator.identifierhttps://orcid.org/0000-0003-2219-5833
dc.relation.departmentThe Linhardt Research Labs.
dc.relation.departmentThe Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
rpi.description.pages100-107
rpi.description.volume28


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Except where otherwise noted, this item's license is described as CC0 — Public Domain