Kinetics and crystal structure of human purine nucleoside phosphorylase in complex with 7-methyl-6-thio-guanosine

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dc.contributor.authorSilva, Rafael G.
dc.contributor.authorPereira, José H. [UNESP]
dc.contributor.authorCanduri, Fernanda [UNESP]
dc.contributor.authorDe Azevedo Jr., Walter F. [UNESP]
dc.contributor.authorBasso, Luiz A.
dc.contributor.authorSantos, Diógenes S.
dc.contributor.institutionPontifícia Universidade Católica do Rio Grande do Sul (PUCRS)
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2014-05-27T11:21:37Z
dc.date.available2014-05-27T11:21:37Z
dc.date.issued2005-10-01
dc.description.abstractPurine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of nucleosides and deoxynucleosides, generating ribose 1-phosphate and the purine base, which is an important step of purine catabolism pathway. The lack of such an activity in humans, owing to a genetic disorder, causes T-cell impairment, and drugs that inhibit this enzyme may have the potential of being utilized as modulators of the immunological system to treat leukemia, autoimmune diseases, and rejection in organ transplantation. Here, we describe kinetics and crystal structure of human PNP in complex with 7-methyl-6-thio-guanosine, a synthetic substrate, which is largely used in activity assays. Analysis of the structure identifies different protein conformational changes upon ligand binding, and comparison of kinetic and structural data permits an understanding of the effects of atomic substitution on key positions of the synthetic substrate and their consequences to enzyme binding and catalysis. Such knowledge may be helpful in designing new PNP inhibitors. © 2005 Elsevier Inc. All rights reserved.en
dc.description.affiliationCentro de Pesquisas Em Biologia Molecular e Funcional Instituto de Pesquisas Biomédicas PUCRS, Porto Alegre, RS
dc.description.affiliationDepartamento de Física UNESP, S. José do Rio Preto, SP
dc.description.affiliationUnespDepartamento de Física UNESP, S. José do Rio Preto, SP
dc.format.extent49-58
dc.identifierhttp://dx.doi.org/10.1016/j.abb.2005.07.021
dc.identifier.citationArchives of Biochemistry and Biophysics, v. 442, n. 1, p. 49-58, 2005.
dc.identifier.doi10.1016/j.abb.2005.07.021
dc.identifier.issn0003-9861
dc.identifier.lattes9424175688206545
dc.identifier.scopus2-s2.0-24944507288
dc.identifier.urihttp://hdl.handle.net/11449/68419
dc.language.isoeng
dc.relation.ispartofArchives of Biochemistry and Biophysics
dc.relation.ispartofjcr3.118
dc.relation.ispartofsjr1,350
dc.rights.accessRightsAcesso restrito
dc.sourceScopus
dc.subjectCrystal structure
dc.subjectDrug design
dc.subjectKinetic mechanism
dc.subjectMESG
dc.subjectPurine nucleoside phosphorylase
dc.subject7 methyl 6 thioguanosine
dc.subjectguanosine derivative
dc.subjectpurine nucleoside phosphorylase
dc.subjectunclassified drug
dc.subjectcatabolism
dc.subjectcatalysis
dc.subjectcatalyst
dc.subjectcrystal structure
dc.subjectenzyme binding
dc.subjectenzyme kinetics
dc.subjectenzyme substrate
dc.subjectenzyme substrate complex
dc.subjectligand binding
dc.subjectpriority journal
dc.subjectprotein conformation
dc.subjectstructure analysis
dc.subjectCatalysis
dc.subjectCrystallography, X-Ray
dc.subjectEnzyme Inhibitors
dc.subjectGuanosine
dc.subjectHumans
dc.subjectKinetics
dc.subjectLigands
dc.subjectPhosphorylation
dc.subjectProtein Binding
dc.subjectProtein Conformation
dc.subjectPurine-Nucleoside Phosphorylase
dc.subjectPurines
dc.subjectRibosemonophosphates
dc.subjectStructure-Activity Relationship
dc.subjectSubstrate Specificity
dc.subjectThionucleosides
dc.subjectThionucleotides
dc.titleKinetics and crystal structure of human purine nucleoside phosphorylase in complex with 7-methyl-6-thio-guanosineen
dc.typeArtigo
dcterms.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
unesp.author.lattes9424175688206545
unesp.campusUniversidade Estadual Paulista (Unesp), Instituto de Biociências Letras e Ciências Exatas, São José do Rio Pretopt

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