A single P115Q mutation modulates specificity in the Corynebacterium pseudotuberculosis arginine repressor

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MetadadosDescriçãoIdioma
Autor(es): dc.contributorUniversidade Estadual Paulista (Unesp)-
Autor(es): dc.contributorBrazilian Center for Research in Energy and Materials (CNPEM)-
Autor(es): dc.creatorMariutti, Ricardo B. [UNESP]-
Autor(es): dc.creatorHernández-González, Jorge E. [UNESP]-
Autor(es): dc.creatorNascimento, Andrey F.Z.-
Autor(es): dc.creatorde Morais, Mariana A.B.-
Autor(es): dc.creatorMurakami, Mario T.-
Autor(es): dc.creatorCarareto, Claudia M.A. [UNESP]-
Autor(es): dc.creatorArni, Raghuvir K. [UNESP]-
Data de aceite: dc.date.accessioned2022-02-22T00:29:45Z-
Data de disponibilização: dc.date.available2022-02-22T00:29:45Z-
Data de envio: dc.date.issued2020-12-11-
Data de envio: dc.date.issued2020-12-11-
Data de envio: dc.date.issued2020-07-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1016/j.bbagen.2020.129597-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/200200-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/200200-
Descrição: dc.descriptionThe arginine repressor (ArgR) regulates the expression of genes involved in arginine biosynthesis. Upon attaining a threshold concentration of arginine in the cytoplasm, the trimeric C-terminal domain of ArgR binds three arginines in a shallow surface cleft and subsequently hexamerizes forming a dimer of trimers containing six Arg co-repressor molecules which are buried at the subunit interfaces. The N-terminal domains of this complex bind to the DNA promoter thereby interrupting the transcription of the genes related to Arg biosynthesis. The crystal structures of the wild type and mutant Pro115Gln ArgR from Corynebacterium pseudotuberculosis determined at 1.7 Å demonstrate that a single amino acid substitution switches co-repressor specificity from Tyr to Arg. Molecular dynamics simulations indicate that the first step, i.e., the binding of the co-repressor, occurs in the trimeric state and that Pro115Gln ArgR preferentially binds Arg. It was also shown that, in Pro115 ArgR hexamers, the concomitant binding of sodium ions shifts selectivity to Tyr. Structural data combined with phylogenetic analyses of ArgR from C. pseudotuberculosis suggest that substitutions in the binding pocket at position 115 may alter its specificity for amino acids and that the length of the protein interdomain linker can provide further functional flexibility. These results support the existence of alternative ArgR regulatory mechanisms in this pathogenic bacterium.-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionMultiuser Center for Biomolecular Innovation IBILCE/UNESP-
Descrição: dc.descriptionDepartment of Physics IBILCE/UNESP-
Descrição: dc.descriptionBrazilian Synchrotron Light Laboratory (LNLS) Brazilian Center for Research in Energy and Materials (CNPEM)-
Descrição: dc.descriptionLaboratory of Molecular Evolution IBILCE/UNESP-
Descrição: dc.descriptionMultiuser Center for Biomolecular Innovation IBILCE/UNESP-
Descrição: dc.descriptionDepartment of Physics IBILCE/UNESP-
Descrição: dc.descriptionLaboratory of Molecular Evolution IBILCE/UNESP-
Descrição: dc.descriptionFAPESP: 2015/13765-0-
Descrição: dc.descriptionFAPESP: 2015/18868-2-
Descrição: dc.descriptionFAPESP: 2016/19995-0-
Descrição: dc.descriptionFAPESP: 2016/24587-9-
Descrição: dc.descriptionFAPESP: 2018/07977-3-
Descrição: dc.descriptionFAPESP: 2018/10736-8-
Idioma: dc.languageen-
Relação: dc.relationBiochimica et Biophysica Acta - General Subjects-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectArginine repressor-
Palavras-chave: dc.subjectCorynebacterium pseudotuberculosis-
Palavras-chave: dc.subjectCrystal structure-
Palavras-chave: dc.subjectFree energy calculations-
Palavras-chave: dc.subjectMD simulations-
Título: dc.titleA single P115Q mutation modulates specificity in the Corynebacterium pseudotuberculosis arginine repressor-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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