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http://purl.uniprot.org/citations/10205157http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/10205157http://www.w3.org/2000/01/rdf-schema#comment"The aspartate-specific caspases are critical protease effectors of programmed cell death and consequently represent important targets for apoptotic intervention. Baculovirus P35 is a potent substrate inhibitor of metazoan caspases, a property that accounts for its unique effectiveness in preventing apoptosis in phylogenetically diverse organisms. Here we report the 2.2 A resolution crystal structure of P35, the first structure of a protein inhibitor of the death caspases. The P35 monomer possesses a solvent-exposed loop that projects from the protein's main beta-sheet core and positions the requisite aspartate cleavage site at the loop's apex. Distortion or destabilization of this reactive site loop by site-directed mutagenesis converted P35 to an efficient substrate which, unlike wild-type P35, failed to interact stably with the target caspase or block protease activity. Thus, cleavage alone is insufficient for caspase inhibition. These data are consistent with a new model wherein the P35 reactive site loop participates in a unique multi-step mechanism in which the spatial orientation of the loop with respect to the P35 core determines post-cleavage association and stoichiometric inhibition of target caspases."xsd:string
http://purl.uniprot.org/citations/10205157http://purl.org/dc/terms/identifier"doi:10.1093/emboj/18.8.2031"xsd:string
http://purl.uniprot.org/citations/10205157http://purl.uniprot.org/core/author"Fisher A.J."xsd:string
http://purl.uniprot.org/citations/10205157http://purl.uniprot.org/core/author"Friesen P.D."xsd:string
http://purl.uniprot.org/citations/10205157http://purl.uniprot.org/core/author"Schneider C.L."xsd:string
http://purl.uniprot.org/citations/10205157http://purl.uniprot.org/core/author"Cruz W.d."xsd:string
http://purl.uniprot.org/citations/10205157http://purl.uniprot.org/core/author"Zoog S.J."xsd:string
http://purl.uniprot.org/citations/10205157http://purl.uniprot.org/core/date"1999"xsd:gYear
http://purl.uniprot.org/citations/10205157http://purl.uniprot.org/core/name"EMBO J"xsd:string
http://purl.uniprot.org/citations/10205157http://purl.uniprot.org/core/pages"2031-2039"xsd:string
http://purl.uniprot.org/citations/10205157http://purl.uniprot.org/core/title"Crystal structure of baculovirus P35: role of a novel reactive site loop in apoptotic caspase inhibition."xsd:string
http://purl.uniprot.org/citations/10205157http://purl.uniprot.org/core/volume"18"xsd:string
http://purl.uniprot.org/citations/10205157http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/10205157
http://purl.uniprot.org/citations/10205157http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/10205157
http://purl.uniprot.org/uniprot/#_P08160-mappedCitation-10205157http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/10205157
http://purl.uniprot.org/uniprot/P08160http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/10205157