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Use este identificador para citar o ir al link de este elemento: http://hdl.handle.net/1843/55506
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Campo DCValorIdioma
dc.creatorVeronica Silva Valadarespt_BR
dc.creatorLuan Carvalho Martinspt_BR
dc.creatorErnesto A. Romanpt_BR
dc.creatorAna Paula Valentept_BR
dc.creatorElio Cinopt_BR
dc.creatorAdolfo Henrique de Moraes Silvapt_BR
dc.date.accessioned2023-06-28T18:55:26Z-
dc.date.available2023-06-28T18:55:26Z-
dc.date.issued2021-
dc.citation.volume1865pt_BR
dc.citation.issue9pt_BR
dc.citation.spage129949pt_BR
dc.identifier.doihttps://doi.org/10.1016/j.bbagen.2021.129949pt_BR
dc.identifier.issn0304-4165pt_BR
dc.identifier.urihttp://hdl.handle.net/1843/55506-
dc.description.resumoBackground: The N-terminal domain of Tetracenomycin aromatase/cyclase (TcmN), an enzyme derived from Streptomyces glaucescens, is involved in polyketide cyclization, aromatization, and folding. Polyketides are a diverse class of secondary metabolites produced by certain groups of bacteria, fungi, and plants with various pharmaceutical applications. Examples include antibiotics, such as tetracycline, and anticancer drugs, such as doxorubicin. Because TcmN is a promising enzyme for in vitro production of polyketides, it is important to identify conditions that enhance its thermal resistance and optimize its function. Methods: TcmN unfolding, stability, and dynamics were evaluated by fluorescence spectroscopy, circular dichroism, nuclear magnetic resonance 15N relaxation experiments, and microsecond molecular dynamics (MD) simulations. Results: TcmN thermal resistance was enhanced at low protein and high salt concentrations, was pH-dependent, and denaturation was irreversible. Conformational dynamics on the μs-ms timescale were detected for residues in the substrate-binding cavity, and two predominant conformers representing opened and closed cavity states were observed in the MD simulations. Conclusion: Based on the results, a mechanism was proposed in which the thermodynamics and kinetics of the TcmN conformational equilibrium modulate enzyme function by favoring ligand binding and avoiding aggregation. General significance: Understanding the principles underlying TcmN stability and dynamics may help in designing mutants with optimal properties for biotechnological applications.pt_BR
dc.description.sponsorshipCNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológicopt_BR
dc.description.sponsorshipFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Geraispt_BR
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorpt_BR
dc.description.sponsorshipOutra Agênciapt_BR
dc.languageengpt_BR
dc.publisherUniversidade Federal de Minas Geraispt_BR
dc.publisher.countryBrasilpt_BR
dc.publisher.departmentICX - DEPARTAMENTO DE QUÍMICApt_BR
dc.publisher.initialsUFMGpt_BR
dc.relation.ispartofBiochimica et Biophysica Acta - General Subjectspt_BR
dc.rightsAcesso Restritopt_BR
dc.subjectPolyketidept_BR
dc.subjectAromatase/cyclasept_BR
dc.subjectConformational dynamicspt_BR
dc.subjectAggregationpt_BR
dc.subject.otherEspectroscopia de fluorescênciapt_BR
dc.subject.otherBiossíntesept_BR
dc.subject.otherEspectroscopia de ressonância nuclearpt_BR
dc.subject.otherAnálise conformacionalpt_BR
dc.subject.otherDicroismo circularpt_BR
dc.subject.otherProteínas - Síntesept_BR
dc.titleConformational dynamics of tetracenomycin aromatase/cyclase regulate polyketide binding and enzyme aggregation propensitypt_BR
dc.typeArtigo de Periódicopt_BR
dc.url.externahttps://www.sciencedirect.com/science/article/pii/S0304416521001070?via%3Dihubpt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-3344-4084pt_BR
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