Structure of shikimate kinase from Mycobacterium tuberculosis reveals the binding of shikimic acid

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dc.contributor.authorPereira, J. H.
dc.contributor.authorde Oliveira, J. S.
dc.contributor.authorCanduri, F.
dc.contributor.authorDias, MVB
dc.contributor.authorPalma, Mario Sergio [UNESP]
dc.contributor.authorBasso, L. A.
dc.contributor.authorSantos, D. S.
dc.contributor.authorde Azevedo, W. F.
dc.contributor.institutionPontificia Univ Catolica Rio Grande do Sul
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversidade Federal do Rio Grande do Sul (UFRGS)
dc.contributor.institutionInstituto Butantan
dc.date.accessioned2014-05-20T13:54:34Z
dc.date.available2014-05-20T13:54:34Z
dc.date.issued2004-12-01
dc.description.abstractTuberculosis made a resurgence in the mid-1980s and now kills approximately 3 million people a year. The re-emergence of tuberculosis as a public health threat, the high susceptibility of HIV-infected persons and the proliferation of multi-drug-resistant strains have created a need to develop new drugs. Shikimate kinase and other enzymes in the shikimate pathway are attractive targets for development of non-toxic antimicrobial agents, herbicides and anti-parasitic drugs, because the pathway is essential in these species whereas it is absent from mammals. The crystal structure of shikimate kinase from Mycobacterium tuberculosis (MtSK) complexed with MgADP and shikimic acid ( shikimate) has been determined at 2.3 Angstrom resolution, clearly revealing the amino-acid residues involved in shikimate binding. This is the first three-dimensional structure of shikimate kinase complexed with shikimate. In MtSK, the Glu61 residue that is strictly conserved in shikimate kinases forms a hydrogen bond and salt bridge with Arg58 and assists in positioning the guanidinium group of Arg58 for shikimate binding. The carboxyl group of shikimate interacts with Arg58, Gly81 and Arg136 and the hydroxyl groups interact with Asp34 and Gly80. The crystal structure of MtSK-MgADP-shikimate will provide crucial information for the elucidation of the mechanism of the shikimate kinase-catalyzed reaction and for the development of a new generation of drugs against tuberculosis.en
dc.description.affiliationPontificia Univ Catolica Rio Grande do Sul, Ctr Pesquisas & Desenvolvimento Biol Mol & Func, BR-90619900 Porto Alegre, RS, Brazil
dc.description.affiliationUNESP, Dept Fis, Programa Posgrad Biofis Mol, BR-15054000 Sao Jose do Rio Preto, SP, Brazil
dc.description.affiliationUniv Fed Rio Grande do Sul, Dept Biol Mol & Biotecnol, Rede Brasileira Pesquisa TB Grp Microbiol Mol & F, BR-91501970 Porto Alegre, RS, Brazil
dc.description.affiliationInst Butantan, Ctr Appl Toxinol, BR-05503900 São Paulo, Brazil
dc.description.affiliationUNESP, Inst Biosci, CEIS Dept Biol, Lab Struct Biol & Zoochem, BR-13506900 Rio Claro, SP, Brazil
dc.description.affiliationUnespUNESP, Dept Fis, Programa Posgrad Biofis Mol, BR-15054000 Sao Jose do Rio Preto, SP, Brazil
dc.description.affiliationUnespUNESP, Inst Biosci, CEIS Dept Biol, Lab Struct Biol & Zoochem, BR-13506900 Rio Claro, SP, Brazil
dc.format.extent2310-2319
dc.identifierhttp://dx.doi.org/10.1107/S090744490402517X
dc.identifier.citationActa Crystallographica Section D-biological Crystallography. Malden: Wiley-blackwell, v. 60, p. 2310-2319, 2004.
dc.identifier.doi10.1107/S090744490402517X
dc.identifier.issn0907-4449
dc.identifier.lattes2901888624506535
dc.identifier.urihttp://hdl.handle.net/11449/19522
dc.identifier.wosWOS:000225360800003
dc.language.isoeng
dc.publisherWiley-Blackwell
dc.relation.ispartofActa Crystallographica Section D: Biological Crystallography
dc.rights.accessRightsAcesso restrito
dc.sourceWeb of Science
dc.titleStructure of shikimate kinase from Mycobacterium tuberculosis reveals the binding of shikimic aciden
dc.typeArtigo
dcterms.licensehttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dcterms.rightsHolderWiley-Blackwell
unesp.author.lattes2901888624506535
unesp.author.orcid0000-0002-5312-0191[4]
unesp.author.orcid0000-0002-7363-8211[5]
unesp.author.orcid0000-0003-0903-2407[6]
unesp.author.orcid0000-0003-4971-463X[7]
unesp.campusUniversidade Estadual Paulista (Unesp), Instituto de Biociências, Rio Claropt
unesp.campusUniversidade Estadual Paulista (Unesp), Instituto de Biociências Letras e Ciências Exatas, São José do Rio Pretopt

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