Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/109327
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Mendes, Vítor | - |
dc.contributor.author | Blaszczyk, Michal | - |
dc.contributor.author | Maranha, Ana | - |
dc.contributor.author | Empadinhas, Nuno | - |
dc.contributor.author | Blundell, Tom L. | - |
dc.date.accessioned | 2023-10-10T11:00:54Z | - |
dc.date.available | 2023-10-10T11:00:54Z | - |
dc.date.issued | 2015-11-30 | - |
dc.identifier.issn | 2045-2322 | pt |
dc.identifier.uri | https://hdl.handle.net/10316/109327 | - |
dc.description.abstract | GlgE, an enzyme of the pathway that converts trehalose to α-glucans, is essential for Mycobacterium tuberculosis. Inhibition of GlgE, which transfers maltose from a maltose-1-phosphate donor to α-glucan/maltooligosaccharide chain acceptor, leads to a toxic accumulation of maltose-1-phosphate that culminates in cellular death. Here we describe the first high-resolution mycobacterial GlgE structure from Mycobacterium thermoresistibile at 1.96 Å. We show that the structure resembles that of M. tuberculosis and Streptomyces coelicolor GlgEs, reported before, with each protomer in the homodimer comprising five domains. However, in M. thermoresistibile GlgE we observe several conformational states of the S domain and provide evidence that its high flexibility is important for enzyme activity. The structures here reported shed further light on the interactions between the N-terminal domains and the catalytic domains of opposing chains and how they contribute to the catalytic reaction. Importantly this work identifies a useful surrogate system to aid the development of GlgE inhibitors against opportunistic and pathogenic mycobacteria. | pt |
dc.language.iso | eng | pt |
dc.publisher | Springer Nature | pt |
dc.relation | Bill & Melinda Gates Foundation (subcontract by the Foundation for the National Institutes of Health - NIH) (OPP1024021) | pt |
dc.relation | Fundação para a Ciência e a Tecnologia through EU-FEDER-COMPETE(FCOMP-01-0124-FEDER-028359 [PTDC/ BIA-MIC/2779/2012] | pt |
dc.relation | SFRH/BPD/79531/2011 | pt |
dc.relation | SFRH/BD/74845/2010 | pt |
dc.rights | openAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt |
dc.subject.mesh | Bacterial Proteins | pt |
dc.subject.mesh | Binding Sites | pt |
dc.subject.mesh | Catalysis | pt |
dc.subject.mesh | Catalytic Domain | pt |
dc.subject.mesh | Crystallography, X-Ray | pt |
dc.subject.mesh | Glucosyltransferases | pt |
dc.subject.mesh | Kinetics | pt |
dc.subject.mesh | Maltose | pt |
dc.subject.mesh | Mycobacterium | pt |
dc.subject.mesh | Phosphorylation | pt |
dc.subject.mesh | Protein Interaction Domains and Motifs | pt |
dc.subject.mesh | Structure-Activity Relationship | pt |
dc.subject.mesh | Sugar Phosphates | pt |
dc.subject.mesh | Models, Molecular | pt |
dc.subject.mesh | Protein Conformation | pt |
dc.title | Structure of Mycobacterium thermoresistibile GlgE defines novel conformational states that contribute to the catalytic mechanism | pt |
dc.type | article | - |
degois.publication.firstPage | 17144 | pt |
degois.publication.issue | 1 | pt |
degois.publication.title | Scientific Reports | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.1038/srep17144 | pt |
degois.publication.volume | 5 | pt |
dc.date.embargo | 2015-11-30 | * |
uc.date.periodoEmbargo | 0 | pt |
item.grantfulltext | open | - |
item.cerifentitytype | Publications | - |
item.languageiso639-1 | en | - |
item.openairetype | article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | Com Texto completo | - |
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-Mycobacterium-thermoresistibile-GlgE-defines-novel-conformational-states-that-contribute-to-the-catalytic-mechanismScientific-Reports.pdf | 3.53 MB | Adobe PDF | View/Open |
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