Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/109319
DC Field | Value | Language |
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dc.contributor.author | Fraga, Joana | - |
dc.contributor.author | Maranha, Ana | - |
dc.contributor.author | Mendes, Vítor | - |
dc.contributor.author | Pereira, Pedro José Barbosa | - |
dc.contributor.author | Empadinhas, Nuno | - |
dc.contributor.author | Macedo-Ribeiro, Sandra | - |
dc.date.accessioned | 2023-10-10T10:36:49Z | - |
dc.date.available | 2023-10-10T10:36:49Z | - |
dc.date.issued | 2015-01-26 | - |
dc.identifier.issn | 2045-2322 | pt |
dc.identifier.uri | https://hdl.handle.net/10316/109319 | - |
dc.description.abstract | A 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.sponsorship | This 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.iso | eng | pt |
dc.publisher | Springer Nature | pt |
dc.relation | PTDC/BIA-PRO/110523/2009 | pt |
dc.relation | PTDC/BIA-BCM/112459/2009 | pt |
dc.relation | PTDC/BIA-MIC/2779/2012 | pt |
dc.relation | PEst-C/SAU/LA0001/2013 | pt |
dc.relation | SFRH/BD/74845/2010 | pt |
dc.relation | SFRH/BPD/79531/2011 | pt |
dc.rights | openAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt |
dc.subject.mesh | Adenosine Triphosphate | pt |
dc.subject.mesh | Glucosyltransferases | pt |
dc.subject.mesh | Kinetics | pt |
dc.subject.mesh | Metabolic Networks and Pathways | pt |
dc.subject.mesh | Mycobacterium tuberculosis | pt |
dc.subject.mesh | Phosphotransferases (Alcohol Group Acceptor) | pt |
dc.subject.mesh | Phylogeny | pt |
dc.subject.mesh | Protein Folding | pt |
dc.subject.mesh | Protein Structure, Quaternary | pt |
dc.title | Structure of mycobacterial maltokinase, the missing link in the essential GlgE-pathway | pt |
dc.type | article | - |
degois.publication.firstPage | 8026 | pt |
degois.publication.issue | 1 | pt |
degois.publication.title | Scientific Reports | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.1038/srep08026 | pt |
degois.publication.volume | 5 | pt |
dc.date.embargo | 2015-01-26 | * |
uc.date.periodoEmbargo | 0 | pt |
item.languageiso639-1 | en | - |
item.fulltext | Com Texto completo | - |
item.grantfulltext | open | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.openairetype | article | - |
item.cerifentitytype | Publications | - |
crisitem.project.grantno | Strategic Project - LA 1 - 2013-2014 | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.orcid | 0000-0001-9005-8377 | - |
crisitem.author.orcid | 0000-0001-8938-7560 | - |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais |
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File | Description | Size | Format | |
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Structure-of-mycobacterial-maltokinase-the-missing-link-in-the-essential-GlgEpathwayScientific-Reports.pdf | 2.54 MB | Adobe PDF | View/Open |
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