Chorismate synthase: An attractive target for drug development against orphan diseases

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dc.contributor.authorDias, Marcio V.B. [UNESP]
dc.contributor.authorEly, Fernanda
dc.contributor.authorPalma, Mario Sergio [UNESP]
dc.contributor.authorAzevedo Jr., Walter F. de
dc.contributor.authorBasso, Luiz A.
dc.contributor.authorSantos, Diógenes S.
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionPontifícia Universidade Católica do Rio Grande do Sul (PUCRS)
dc.date.accessioned2014-05-27T11:22:25Z
dc.date.available2014-05-27T11:22:25Z
dc.date.issued2007-03-01
dc.description.abstractThe increase in incidence of infectious diseases worldwide, particularly in developing countries, is worrying. Each year, 14 million people are killed by infectious diseases, mainly HIV/AIDS, respiratory infections, malaria and tuberculosis. Despite the great burden in the poor countries, drug discovery to treat tropical diseases has come to a standstill. There is no interest by the pharmaceutical industry in drug development against the major diseases of the poor countries, since the financial return cannot be guaranteed. This has created an urgent need for new therapeutics to neglected diseases. A possible approach has been the exploitation of the inhibition of unique targets, vital to the pathogen such as the shikimate pathway enzymes, which are present in bacteria, fungi and apicomplexan parasites but are absent in mammals. The chorismate synthase (CS) catalyses the seventh step in this pathway, the conversion of 5-enolpyruvylshikimate-3-phosphate to chorismate. The strict requirement for a reduced flavin mononucleotide and the anti 1,4 elimination are both unusual aspects which make CS reaction unique among flavin-dependent enzymes, representing an important target for the chemotherapeutic agents development. In this review we present the main biochemical features of CS from bacterial and fungal sources and their difference from the apicomplexan CS. The CS mechanisms proposed are discussed and compared with structural data. The CS structures of some organisms are compared and their distinct features analyzed. Some known CS inhibitors are presented and the main characteristics are discussed. The structural and kinetics data reviewed here can be useful for the design of inhibitors. © 2007 Bentham Science Publishers Ltd.en
dc.description.affiliationPrograma de Pós-Graduação em Biofísica Molecular Departamento de Física UNESP, Sao Jose do Rio Preto, SP 15054-000
dc.description.affiliationCentro de Pesquisas em Biologia Molecular e Funcional PUCRS, Avenida Ipiranga 6681, 90619-900 Porto Alegre, RS
dc.description.affiliationDepartamento de Biologia Instituto de Biociências UNESP, Rio Claro, SP 13506-900
dc.description.affiliationFaculdade de Biociências PUCRS, Avenida Ipiranga 6681, 90619-900 Porto Alegre, RS
dc.description.affiliationUnespPrograma de Pós-Graduação em Biofísica Molecular Departamento de Física UNESP, Sao Jose do Rio Preto, SP 15054-000
dc.description.affiliationUnespDepartamento de Biologia Instituto de Biociências UNESP, Rio Claro, SP 13506-900
dc.format.extent437-444
dc.identifierhttp://dx.doi.org/10.2174/138945007780058924
dc.identifier.citationCurrent Drug Targets, v. 8, n. 3, p. 437-444, 2007.
dc.identifier.doi10.2174/138945007780058924
dc.identifier.issn1389-4501
dc.identifier.lattes2901888624506535
dc.identifier.scopus2-s2.0-33847723314
dc.identifier.urihttp://hdl.handle.net/11449/69562
dc.identifier.wosWOS:000244702900006
dc.language.isoeng
dc.relation.ispartofCurrent Drug Targets
dc.relation.ispartofjcr3.112
dc.relation.ispartofsjr0,906
dc.rights.accessRightsAcesso restrito
dc.sourceScopus
dc.subjectChorismate synthase
dc.subjectFlavin-dependent enzymes
dc.subjectInfectious disease
dc.subjectNeglected disease
dc.subjectShikimate pathway
dc.subject6 fluoroshikimic acid
dc.subjectantifungal agent
dc.subjectantiinfective agent
dc.subjectantiparasitic agent
dc.subjectbacterial enzyme
dc.subjectbenzofuran 3[2h] one
dc.subjectchorismate synthase
dc.subjectchorismate synthase inhibitor
dc.subjectenzyme inhibitor
dc.subjectfungal enzyme
dc.subjectreduced nicotinamide adenine dinucleotide phosphate
dc.subjectshikimic acid
dc.subjectshikimic acid derivative
dc.subjectunclassified drug
dc.subjectbacterial infection
dc.subjectbacterial strain
dc.subjectcatalysis
dc.subjectcrystal structure
dc.subjectcrystallization
dc.subjectdrug design
dc.subjectdrug research
dc.subjectdrug synthesis
dc.subjectdrug targeting
dc.subjectenzyme active site
dc.subjectenzyme activity
dc.subjectenzyme analysis
dc.subjectenzyme inhibition
dc.subjectenzyme isolation
dc.subjectenzyme kinetics
dc.subjectenzyme localization
dc.subjectenzyme mechanism
dc.subjectenzyme structure
dc.subjectfungal strain
dc.subjectgenetic code
dc.subjectminimum inhibitory concentration
dc.subjectnonhuman
dc.subjectphylogeny
dc.subjectprotein secondary structure
dc.subjectreview
dc.subjectsite directed mutagenesis
dc.subjectstructure analysis
dc.subjectAnimals
dc.subjectDrug Delivery Systems
dc.subjectEnzyme Inhibitors
dc.subjectHumans
dc.subjectOrphan Drug Production
dc.subjectPhosphorus-Oxygen Lyases
dc.subjectRare Diseases
dc.titleChorismate synthase: An attractive target for drug development against orphan diseasesen
dc.typeResenha
dcterms.licensehttp://eurekaselect.com/209
unesp.author.lattes2901888624506535
unesp.author.orcid0000-0002-5312-0191[1]
unesp.author.orcid0000-0002-2866-5704[2]
unesp.author.orcid0000-0002-7363-8211[3]
unesp.author.orcid0000-0003-4971-463X[6]
unesp.author.orcid0000-0003-0903-2407[5]
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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Artigos - Física - IBILCE
Artigos - Biologia - IBRC