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dc.contributor.authorVivan, Ana Luiza
dc.contributor.authorCaceres, Rafael Andrade
dc.contributor.authorBeltran Abrego, Jose Ramon [UNESP]
dc.contributor.authorBorges, Julio Cesar
dc.contributor.authorNeto, Joao Ruggiero [UNESP]
dc.contributor.authorRamos, Carlos H. I.
dc.contributor.authorde Azevedo, Walter Filgueira
dc.contributor.authorBasso, Luiz Augusto
dc.contributor.authorSantos, Diogenes Santiago
dc.identifier.citationProteins-structure Function and Bioinformatics. Malden: Wiley-blackwell, v. 72, n. 4, p. 1352-1362, 2008.
dc.description.abstractTuberculosis (TB) is one of the most common infectious diseases known to man and responsible for millions of human deaths in the world. The increasing incidence of TB in developing countries, the proliferation of multidrug resistant strains, and the absence of resources for treatment have highlighted the need of developing new drugs against TB. The shikimate pathway leads to the biosynthesis of chorismate, a precursor of aromatic amino acids. This pathway is absent from mammals and shown to be essential for the survival of Mycobacterium tuberculosis, the causative agent of TB. Accordingly, enzymes of aromatic amino acid biosynthesis pathway represent promising targets for structure-based drug design. The first reaction in phenylalanine biosynthesis involves the conversion of chorismate to prephenate, catalyzed by chorismate mutase. The second reaction is catalyzed by prephenate dehydratase (PDT) and involves decarboxylation and dehydratation of prephenate to form phenylpyruvate, the precursor of phenylalanine. Here, we describe utilization of different techniques to infer the structure of M. tuberculosis PDT (MtbPDT) in solution. Small angle X-ray scattering and ultracentrifugation analysis showed that the protein oligomeric state is a tetramer and MtbPDT is a flat disk protein. Bioinformatics tools were used to infer the structure of MtbPDT A molecular model for MtbPDT is presented and molecular dynamics simulations indicate that MtbPDT i.s stable. Experimental and molecular modeling results were in agreement and provide evidence for a tetrameric state of MtbPDT in solution.en
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.relation.ispartofProteins: Structure, Function and Bioinformatics
dc.sourceWeb of Science
dc.subjectMolecular modelingen
dc.subjectsmall-angle X-ray scatteringen
dc.subjectMolecular dynamicsen
dc.subjectanalytical ultracentrifugationen
dc.subjectoligomeric stateen
dc.subjectthree-dimensional structureen
dc.subjectCircular dichroismen
dc.titleStructural studies of prephenate dehydratase from Mycobacterium tuberculosis H37Rv by SAXS, ultracentrifugation, and computational analysisen
dc.contributor.institutionPontifícia Universidade Católica do Rio Grande do Sul (PUCRS)
dc.contributor.institutionUniversidade Federal do Rio Grande do Sul (UFRGS)
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.description.affiliationPontificia Univ Catolica do Rio Grande do Sul, Ctr Pesquisas Biol Mol & Funct, Inst Pesquisas Biomed, BR-90619900 Porto Alegre, RS, Brazil
dc.description.affiliationUniversidade Federal do Rio Grande do Sul (UFRGS), Dept Genet, Programa Pos Graduacao Genet & Biol Mol, Porto Alegre, RS, Brazil
dc.description.affiliationPontificia Univ Catolica do Rio Grande de Sul, Fac Biociencias, Porto Alegre, RS, Brazil
dc.description.affiliationPontificia Univ Catolica do Rio Grande do Sul, Programa Pos Gradaucao Biol Celular & Mol, Porto Alegre, RS, Brazil
dc.description.affiliationUniv Estadual Paulista, IBILCE, Dept Fis, São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Inst Quim São Carlos, Dept Quim & Fis Mol, São Paulo, Brazil
dc.description.affiliationUniv Estadual Campinas, Inst Quim, São Paulo, Brazil
dc.description.affiliationUnespUniv Estadual Paulista, IBILCE, Dept Fis, São Paulo, Brazil
dc.rights.accessRightsAcesso restrito
unesp.campusUniversidade Estadual Paulista (UNESP), Instituto de Biociências Letras e Ciências Exatas, São José do Rio Pretopt
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