Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/109319
DC FieldValueLanguage
dc.contributor.authorFraga, Joana-
dc.contributor.authorMaranha, Ana-
dc.contributor.authorMendes, Vítor-
dc.contributor.authorPereira, Pedro José Barbosa-
dc.contributor.authorEmpadinhas, Nuno-
dc.contributor.authorMacedo-Ribeiro, Sandra-
dc.date.accessioned2023-10-10T10:36:49Z-
dc.date.available2023-10-10T10:36:49Z-
dc.date.issued2015-01-26-
dc.identifier.issn2045-2322pt
dc.identifier.urihttps://hdl.handle.net/10316/109319-
dc.description.abstractA novel four-step pathway identified recently in mycobacteria channels trehalose to glycogen synthesis and is also likely involved in the biosynthesis of two other crucial polymers: intracellular methylglucose lipopolysaccharides and exposed capsular glucan. The structures of three of the intervening enzymes - GlgB, GlgE, and TreS - were recently reported, providing the first templates for rational drug design. Here we describe the structural characterization of the fourth enzyme of the pathway, mycobacterial maltokinase (Mak), uncovering a eukaryotic-like kinase (ELK) fold, similar to methylthioribose kinases and aminoglycoside phosphotransferases. The 1.15 Å structure of Mak in complex with a non-hydrolysable ATP analog reveals subtle structural rearrangements upon nucleotide binding in the cleft between the N- and the C-terminal lobes. Remarkably, this new family of ELKs has a novel N-terminal domain topologically resembling the cystatin family of protease inhibitors. By interfacing with and restraining the mobility of the phosphate-binding region of the N-terminal lobe, Mak's unusual N-terminal domain might regulate its phosphotransfer activity and represents the most likely anchoring point for TreS, the upstream enzyme in the pathway. By completing the gallery of atomic-detail models of an essential pathway, this structure opens new avenues for the rational design of alternative anti-tubercular compounds.pt
dc.description.sponsorshipThis work was funded by national funds through Fundaça˜o para a Cieˆncia e a Tecnologia (FCT) and by EU-FEDER funding through Programa Operacional Regional do Norte (ON.2 - O Novo Quadro de Refereˆncia Estrate´gico Nacional – QREN (grant NORTE-07-0124-FEDER-000002 - Host-Pathogen Interactions), and through the Operational Competitiveness Programme – COMPETE (grants FCOMP-01-0124-FEDER-014321 [PTDC/BIA-PRO/110523/2009], FCOMP-01-0124-FEDER-014187 [PTDC/BIA-BCM/112459/2009], FCOMP-01-0124-FEDER-028359 [PTDC/BIA-MIC/2779/2012], and FCOMP-01-0124-FEDER-037276 [PEst-C/SAU/LA0001/2013-2014]). The financial support of FCT through fellowships SFRH/BD/74845/2010 (A.M.) and SFRH/BPD/79531/ 2011 (V.M.) is also acknowledged.pt
dc.language.isoengpt
dc.publisherSpringer Naturept
dc.relationPTDC/BIA-PRO/110523/2009pt
dc.relationPTDC/BIA-BCM/112459/2009pt
dc.relationPTDC/BIA-MIC/2779/2012pt
dc.relationPEst-C/SAU/LA0001/2013pt
dc.relationSFRH/BD/74845/2010pt
dc.relationSFRH/BPD/79531/2011pt
dc.rightsopenAccesspt
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt
dc.subject.meshAdenosine Triphosphatept
dc.subject.meshGlucosyltransferasespt
dc.subject.meshKineticspt
dc.subject.meshMetabolic Networks and Pathwayspt
dc.subject.meshMycobacterium tuberculosispt
dc.subject.meshPhosphotransferases (Alcohol Group Acceptor)pt
dc.subject.meshPhylogenypt
dc.subject.meshProtein Foldingpt
dc.subject.meshProtein Structure, Quaternarypt
dc.titleStructure of mycobacterial maltokinase, the missing link in the essential GlgE-pathwaypt
dc.typearticle-
degois.publication.firstPage8026pt
degois.publication.issue1pt
degois.publication.titleScientific Reportspt
dc.peerreviewedyespt
dc.identifier.doi10.1038/srep08026pt
degois.publication.volume5pt
dc.date.embargo2015-01-26*
uc.date.periodoEmbargo0pt
item.languageiso639-1en-
item.fulltextCom Texto completo-
item.grantfulltextopen-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.openairetypearticle-
item.cerifentitytypePublications-
crisitem.project.grantnoStrategic Project - LA 1 - 2013-2014-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.orcid0000-0001-9005-8377-
crisitem.author.orcid0000-0001-8938-7560-
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais
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