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http://purl.uniprot.org/citations/21087925http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21087925http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21087925http://www.w3.org/2000/01/rdf-schema#comment"The biosynthetic shikimate pathway consists of seven enzymes that catalyze sequential reactions to generate chorismate, a critical branch point in the synthesis of the aromatic amino acids. The third enzyme in the pathway, dehydroquinate dehydratase (DHQD), catalyzes the dehydration of 3-dehydroquinate to 3-dehydroshikimate. We present three crystal structures of the type I DHQD from the intestinal pathogens Clostridium difficile and Salmonella enterica. Structures of the enzyme with substrate and covalent pre- and post-dehydration reaction intermediates provide snapshots of successive steps along the type I DHQD-catalyzed reaction coordinate. These structures reveal that the position of the substrate within the active site does not appreciably change upon Schiff base formation. The intermediate state structures reveal a reaction state-dependent behavior of His-143 in which the residue adopts a conformation proximal to the site of catalytic dehydration only when the leaving group is present. We speculate that His-143 is likely to assume differing catalytic roles in each of its observed conformations. One conformation of His-143 positions the residue for the formation/hydrolysis of the covalent Schiff base intermediates, whereas the other conformation positions the residue for a role in the catalytic dehydration event. The fact that the shikimate pathway is absent from humans makes the enzymes of the pathway potential targets for the development of non-toxic antimicrobials. The structures and mechanistic insight presented here may inform the design of type I DHQD enzyme inhibitors."xsd:string
http://purl.uniprot.org/citations/21087925http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m110.192831"xsd:string
http://purl.uniprot.org/citations/21087925http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m110.192831"xsd:string
http://purl.uniprot.org/citations/21087925http://purl.uniprot.org/core/author"Anderson W.F."xsd:string
http://purl.uniprot.org/citations/21087925http://purl.uniprot.org/core/author"Anderson W.F."xsd:string
http://purl.uniprot.org/citations/21087925http://purl.uniprot.org/core/author"Lavie A."xsd:string
http://purl.uniprot.org/citations/21087925http://purl.uniprot.org/core/author"Lavie A."xsd:string
http://purl.uniprot.org/citations/21087925http://purl.uniprot.org/core/author"Caffrey M."xsd:string
http://purl.uniprot.org/citations/21087925http://purl.uniprot.org/core/author"Caffrey M."xsd:string
http://purl.uniprot.org/citations/21087925http://purl.uniprot.org/core/author"Minasov G."xsd:string
http://purl.uniprot.org/citations/21087925http://purl.uniprot.org/core/author"Minasov G."xsd:string
http://purl.uniprot.org/citations/21087925http://purl.uniprot.org/core/author"Duban M.E."xsd:string
http://purl.uniprot.org/citations/21087925http://purl.uniprot.org/core/author"Duban M.E."xsd:string
http://purl.uniprot.org/citations/21087925http://purl.uniprot.org/core/author"Light S.H."xsd:string
http://purl.uniprot.org/citations/21087925http://purl.uniprot.org/core/author"Light S.H."xsd:string
http://purl.uniprot.org/citations/21087925http://purl.uniprot.org/core/author"Shuvalova L."xsd:string
http://purl.uniprot.org/citations/21087925http://purl.uniprot.org/core/author"Shuvalova L."xsd:string
http://purl.uniprot.org/citations/21087925http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/21087925http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/21087925http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/21087925http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/21087925http://purl.uniprot.org/core/pages"3531-3539"xsd:string
http://purl.uniprot.org/citations/21087925http://purl.uniprot.org/core/pages"3531-3539"xsd:string