Crystal structure and molecular dynamics studies of human purine nucleoside phosphorylase complexed with 7-deazaguanine

dc.creatorCaceres, RA
dc.creatorTimmers, LFSM
dc.creatorPauli, I
dc.creatorGava, LM
dc.creatorDucati, RG
dc.creatorBasso, LA
dc.creatorSantos, DS
dc.creatorde Azevedo, WF
dc.date2010
dc.dateMAR
dc.date2014-11-15T21:35:15Z
dc.date2015-11-26T17:22:04Z
dc.date2014-11-15T21:35:15Z
dc.date2015-11-26T17:22:04Z
dc.date.accessioned2018-03-29T00:09:33Z
dc.date.available2018-03-29T00:09:33Z
dc.identifierJournal Of Structural Biology. Academic Press Inc Elsevier Science, v. 169, n. 3, n. 379, n. 388, 2010.
dc.identifier1047-8477
dc.identifierWOS:000275296100014
dc.identifier10.1016/j.jsb.2009.11.010
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/57438
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/57438
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/57438
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1283520
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionIn humans, purine nucleoside phosphorylase (HsPNP) is responsible for degradation of deoxyguanosine, and genetic deficiency of this enzyme leads to profound T-cell mediated immunosuppression. HsPNP is a target for inhibitor development aiming at T-cell immune response modulation. Here we report the crystal structure of HsPNP in complex with 7-deazaguanine (HsPNP:7DG) at 2.75 angstrom. Molecular dynamics simulations were employed to assess the structural features of HsPNP in both free form and in complex with 7DG. Our results show that some regions, responsible for entrance and exit of substrate, present a conformational variability, which is dissected by dynamics simulation analysis. Enzymatic assays were also carried out and revealed that 7-deazaguanine presents a lower inhibitory activity against HsPNP (K(i) = 200 mu M). The present structure may be employed in both structure-based design of PNP inhibitors and in development of specific empirical scoring functions. (C) 2009 Elsevier Inc. All rights reserved.
dc.description169
dc.description3
dc.description379
dc.description388
dc.descriptionNational Institute of Science and Technology on Tuberculosis
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionCNPq [300851/98-7, 304051/1975-06, 520182/99-5]
dc.languageen
dc.publisherAcademic Press Inc Elsevier Science
dc.publisherSan Diego
dc.publisherEUA
dc.relationJournal Of Structural Biology
dc.relationJ. Struct. Biol.
dc.rightsfechado
dc.rightshttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.sourceWeb of Science
dc.subjectPurine nucleoside phosphorylase
dc.subject7-Deazaguanine
dc.subjectMolecular dynamics
dc.subjectVirtual screening
dc.subjectX-ray diffraction
dc.subjectEnzymatic assay
dc.subjectLymphocyte Function
dc.subjectDeficiency
dc.subjectSimulations
dc.subjectKinetics
dc.subjectProgram
dc.subjectDocking
dc.subjectSystems
dc.subjectPnp
dc.titleCrystal structure and molecular dynamics studies of human purine nucleoside phosphorylase complexed with 7-deazaguanine
dc.typeArtículos de revistas


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