Structural studies of prephenate dehydratase from Mycobacterium tuberculosis H37Rv by SAXS, ultracentrifugation, and computational analysis

dc.contributorUniversidade Estadual Paulista (UNESP)
dc.creatorVivan, Ana Luiza
dc.creatorCaceres, Rafael Andrade
dc.creatorBeltran Abrego, Jose Ramon
dc.creatorBorges, Julio Cesar
dc.creatorNeto, Joao Ruggiero
dc.creatorRamos, Carlos H. I.
dc.creatorde Azevedo, Walter Filgueira
dc.creatorBasso, Luiz Augusto
dc.creatorSantos, Diogenes Santiago
dc.date2014-05-20T14:02:29Z
dc.date2016-10-25T17:09:08Z
dc.date2014-05-20T14:02:29Z
dc.date2016-10-25T17:09:08Z
dc.date2008-09-01
dc.date.accessioned2017-04-05T21:27:39Z
dc.date.available2017-04-05T21:27:39Z
dc.identifierProteins-structure Function and Bioinformatics. Malden: Wiley-blackwell, v. 72, n. 4, p. 1352-1362, 2008.
dc.identifier0887-3585
dc.identifierhttp://hdl.handle.net/11449/22026
dc.identifierhttp://acervodigital.unesp.br/handle/11449/22026
dc.identifier10.1002/prot.22034
dc.identifierWOS:000259287500021
dc.identifierhttp://dx.doi.org/10.1002/prot.22034
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/867494
dc.descriptionTuberculosis (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.
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.languageeng
dc.publisherWiley-Blackwell
dc.relationProteins: Structure, Function and Bioinformatics
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectMolecular modeling
dc.subjectsmall-angle X-ray scattering
dc.subjectMolecular dynamics
dc.subjectanalytical ultracentrifugation
dc.subjectoligomeric state
dc.subjectBioinformatics
dc.subjectthree-dimensional structure
dc.subjectCircular dichroism
dc.titleStructural studies of prephenate dehydratase from Mycobacterium tuberculosis H37Rv by SAXS, ultracentrifugation, and computational analysis
dc.typeOtro


Este ítem pertenece a la siguiente institución