Crystal Structures of a Plant Trypsin Inhibitor from Enterolobium contortisiliquum (EcTI) and of Its Complex with Bovine Trypsin

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dc.contributor.authorZhou, Dongwen
dc.contributor.authorLobo, Yara A. [UNIFESP]
dc.contributor.authorBatista, Isabel F. C.
dc.contributor.authorMarques-Porto, Rafael
dc.contributor.authorGustchina, Alla
dc.contributor.authorOliva, Maria Luiza Vilela [UNIFESP]
dc.contributor.authorWlodawer, Alexander
dc.contributor.institutionNCI
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionInst Butantan
dc.date.accessioned2016-01-24T14:31:35Z
dc.date.available2016-01-24T14:31:35Z
dc.date.issued2013-04-23
dc.description.abstractA serine protease inhibitor from Enterolobium contortisiliquum (EcTI) belongs to the Kunitz family of plant inhibitors, common in plant seeds. It was shown that EcTI inhibits the invasion of gastric cancer cells through alterations in integrin-dependent cell signaling pathway. We determined high-resolution crystal structures of free EcTI (at 1.75 angstrom) and complexed with bovine trypsin (at 2 angstrom). High quality of the resulting electron density maps and the redundancy of structural information indicated that the sequence of the crystallized isoform contained 176 residues and differed from the one published previously. the structure of the complex confirmed the standard inhibitory mechanism in which the reactive loop of the inhibitor is docked into trypsin active site with the side chains of Arg64 and Ile65 occupying the S1 and S1' pockets, respectively. the overall conformation of the reactive loop undergoes only minor adjustments upon binding to trypsin. Larger deviations are seen in the vicinity of Arg64, driven by the needs to satisfy specificity requirements. A comparison of the EcTI-trypsin complex with the complexes of related Kunitz inhibitors has shown that rigid body rotation of the inhibitors by as much as 15 degrees is required for accurate juxtaposition of the reactive loop with the active site while preserving its conformation. Modeling of the putative complexes of EcTI with several serine proteases and a comparison with equivalent models for other Kunitz inhibitors elucidated the structural basis for the fine differences in their specificity, providing tools that might allow modification of their potency towards the individual enzymes.en
dc.description.affiliationNCI, Ctr Canc Res, Macromol Crystallog Lab, Frederick, MD 21701 USA
dc.description.affiliationUniversidade Federal de São Paulo, Dept Bioquim, São Paulo, Brazil
dc.description.affiliationInst Butantan, Lab Bioquim & Biofis, Unidade Sequenciamento Prot & Peptideos, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Bioquim, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipUnited States Department of Energy, Office of Science, Office of Basic Energy Sciences
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipNational Institutes of Health, National Cancer Institute, Center for Cancer Research
dc.description.sponsorshipIDUnited States Department of Energy, Office of Science, Office of Basic Energy Sciences: W-31-109-Eng-38
dc.description.sponsorshipIDFAPESP: 09/53766-5
dc.format.extent15
dc.identifierhttp://dx.doi.org/10.1371/journal.pone.0062252
dc.identifier.citationPlos One. San Francisco: Public Library Science, v. 8, n. 4, 15 p., 2013.
dc.identifier.doi10.1371/journal.pone.0062252
dc.identifier.fileWOS000318008400158.pdf
dc.identifier.issn1932-6203
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/36216
dc.identifier.wosWOS:000318008400158
dc.language.isoeng
dc.publisherPublic Library Science
dc.relation.ispartofPlos One
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleCrystal Structures of a Plant Trypsin Inhibitor from Enterolobium contortisiliquum (EcTI) and of Its Complex with Bovine Trypsinen
dc.typeinfo:eu-repo/semantics/article
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