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http://purl.uniprot.org/citations/25111069http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25111069http://www.w3.org/2000/01/rdf-schema#comment"Sirtuins are NAD(+)-dependent deacetylases acting as sensors in metabolic pathways and stress response. In mammals there are seven isoforms. The mitochondrial sirtuin 5 is a weak deacetylase but a very efficient demalonylase and desuccinylase; however, its substrate acyl specificity has not been systematically analyzed. Herein, we investigated a carbamoyl phosphate synthetase 1 derived peptide substrate and modified the lysine side chain systematically to determine the acyl specificity of Sirt5. From that point we designed six potent peptide-based inhibitors that interact with the NAD(+) binding pocket. To characterize the interaction details causing the different substrate and inhibition properties we report several X-ray crystal structures of Sirt5 complexed with these peptides. Our results reveal the Sirt5 acyl selectivity and its molecular basis and enable the design of inhibitors for Sirt5."xsd:string
http://purl.uniprot.org/citations/25111069http://purl.org/dc/terms/identifier"doi:10.1002/anie.201402679"xsd:string
http://purl.uniprot.org/citations/25111069http://purl.uniprot.org/core/author"Scharfe M."xsd:string
http://purl.uniprot.org/citations/25111069http://purl.uniprot.org/core/author"Steegborn C."xsd:string
http://purl.uniprot.org/citations/25111069http://purl.uniprot.org/core/author"Roessler C."xsd:string
http://purl.uniprot.org/citations/25111069http://purl.uniprot.org/core/author"Nowak T."xsd:string
http://purl.uniprot.org/citations/25111069http://purl.uniprot.org/core/author"Schutkowski M."xsd:string
http://purl.uniprot.org/citations/25111069http://purl.uniprot.org/core/author"Sippl W."xsd:string
http://purl.uniprot.org/citations/25111069http://purl.uniprot.org/core/author"Nguyen G.T."xsd:string
http://purl.uniprot.org/citations/25111069http://purl.uniprot.org/core/author"Gertz M."xsd:string
http://purl.uniprot.org/citations/25111069http://purl.uniprot.org/core/author"Pannek M."xsd:string
http://purl.uniprot.org/citations/25111069http://purl.uniprot.org/core/author"Born I."xsd:string
http://purl.uniprot.org/citations/25111069http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/25111069http://purl.uniprot.org/core/name"Angew Chem Int Ed Engl"xsd:string
http://purl.uniprot.org/citations/25111069http://purl.uniprot.org/core/pages"10728-10732"xsd:string
http://purl.uniprot.org/citations/25111069http://purl.uniprot.org/core/title"Chemical probing of the human sirtuin 5 active site reveals its substrate acyl specificity and peptide-based inhibitors."xsd:string
http://purl.uniprot.org/citations/25111069http://purl.uniprot.org/core/volume"53"xsd:string
http://purl.uniprot.org/citations/25111069http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/25111069
http://purl.uniprot.org/citations/25111069http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/25111069
http://purl.uniprot.org/uniprot/#_A0A7P0TBF5-mappedCitation-25111069http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25111069
http://purl.uniprot.org/uniprot/#_P31327-mappedCitation-25111069http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25111069
http://purl.uniprot.org/uniprot/#_Q9NXA8-mappedCitation-25111069http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25111069
http://purl.uniprot.org/uniprot/#_Q6DHI5-mappedCitation-25111069http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25111069
http://purl.uniprot.org/uniprot/#_Q7Z3A0-mappedCitation-25111069http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25111069