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http://purl.uniprot.org/citations/15248756http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15248756http://www.w3.org/2000/01/rdf-schema#comment"Arginase is a manganese metalloenzyme that catalyzes the hydrolysis of L-arginine to form L-ornithine and urea. The structure and stability of the binuclear manganese cluster are critical for catalytic activity as it activates the catalytic nucleophile, metal-bridging hydroxide ion, and stabilizes the tetrahedral intermediate and its flanking states. Here, we report X-ray structures of a series of inhibitors bound to the active site of arginase, and each inhibitor exploits a different mode of coordination with the Mn(2+)(2) cluster. Specifically, we have studied the binding of fluoride ion (F(-); an uncompetitive inhibitor) and L-arginine, L-valine, dinor-N(omega)-hydroxy-L-arginine, descarboxy-nor-N(omega)-hydroxy-L-arginine, and dehydro-2(S)-amino-6-boronohexanoic acid. Some inhibitors, such as fluoride ion, dinor-N(omega)-hydroxy-L-arginine, and dehydro-2(S)-amino-6-boronohexanoic acid, cause the net addition of one ligand to the Mn(2+)(2) cluster. Other inhibitors, such as descarboxy-nor-N(omega)-hydroxy-L-arginine, simply displace the metal-bridging hydroxide ion of the native enzyme and do not cause any net change in the metal coordination polyhedra. The highest affinity inhibitors displace the metal-bridging hydroxide ion (and sometimes occupy a Mn(2+)(A) site found vacant in the native enzyme) and maintain a conserved array of hydrogen bonds with their alpha-amino and -carboxylate groups."xsd:string
http://purl.uniprot.org/citations/15248756http://purl.org/dc/terms/identifier"doi:10.1021/bi0491705"xsd:string
http://purl.uniprot.org/citations/15248756http://purl.uniprot.org/core/author"Han S."xsd:string
http://purl.uniprot.org/citations/15248756http://purl.uniprot.org/core/author"Christianson D.W."xsd:string
http://purl.uniprot.org/citations/15248756http://purl.uniprot.org/core/author"Viola R.E."xsd:string
http://purl.uniprot.org/citations/15248756http://purl.uniprot.org/core/author"Ash D.E."xsd:string
http://purl.uniprot.org/citations/15248756http://purl.uniprot.org/core/author"Cama E."xsd:string
http://purl.uniprot.org/citations/15248756http://purl.uniprot.org/core/author"Emig F.A."xsd:string
http://purl.uniprot.org/citations/15248756http://purl.uniprot.org/core/author"Mansuy D."xsd:string
http://purl.uniprot.org/citations/15248756http://purl.uniprot.org/core/author"Boucher J.L."xsd:string
http://purl.uniprot.org/citations/15248756http://purl.uniprot.org/core/author"Pethe S."xsd:string
http://purl.uniprot.org/citations/15248756http://purl.uniprot.org/core/date"2004"xsd:gYear
http://purl.uniprot.org/citations/15248756http://purl.uniprot.org/core/name"Biochemistry"xsd:string
http://purl.uniprot.org/citations/15248756http://purl.uniprot.org/core/pages"8987-8999"xsd:string
http://purl.uniprot.org/citations/15248756http://purl.uniprot.org/core/title"Inhibitor coordination interactions in the binuclear manganese cluster of arginase."xsd:string
http://purl.uniprot.org/citations/15248756http://purl.uniprot.org/core/volume"43"xsd:string
http://purl.uniprot.org/citations/15248756http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/15248756
http://purl.uniprot.org/citations/15248756http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/15248756
http://purl.uniprot.org/uniprot/#_A6JUJ9-mappedCitation-15248756http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15248756
http://purl.uniprot.org/uniprot/#_A6JUK0-mappedCitation-15248756http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15248756
http://purl.uniprot.org/uniprot/#_A6JUK1-mappedCitation-15248756http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15248756
http://purl.uniprot.org/uniprot/#_P07824-mappedCitation-15248756http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15248756
http://purl.uniprot.org/uniprot/A6JUK0http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/15248756
http://purl.uniprot.org/uniprot/A6JUJ9http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/15248756