RDF/XMLNTriplesTurtleShow queryShare
SubjectPredicateObject
http://purl.uniprot.org/citations/10995765http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/10995765http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/10995765http://www.w3.org/2000/01/rdf-schema#comment"Endoplasmic reticulum (ER) class I alpha1,2-mannosidase (also known as ER alpha-mannosidase I) is a critical enzyme in the maturation of N-linked oligosaccharides and ER-associated degradation. Trimming of a single mannose residue acts as a signal to target misfolded glycoproteins for degradation by the proteasome. Crystal structures of the catalytic domain of human ER class I alpha1,2-mannosidase have been determined both in the presence and absence of the potent inhibitors kifunensine and 1-deoxymannojirimycin. Both inhibitors bind to the protein at the bottom of the active-site cavity, with the essential calcium ion coordinating the O-2' and O-3' hydroxyls and stabilizing the six-membered rings of both inhibitors in a (1)C(4) conformation. This is the first direct evidence of the role of the calcium ion. The lack of major conformational changes upon inhibitor binding and structural comparisons with the yeast alpha1, 2-mannosidase enzyme-product complex suggest that this class of inverting enzymes has a novel catalytic mechanism. The structures also provide insight into the specificity of this class of enzymes and provide a blueprint for the future design of novel inhibitors that prevent degradation of misfolded proteins in genetic diseases."xsd:string
http://purl.uniprot.org/citations/10995765http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m006927200"xsd:string
http://purl.uniprot.org/citations/10995765http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m006927200"xsd:string
http://purl.uniprot.org/citations/10995765http://purl.uniprot.org/core/author"Howell P.L."xsd:string
http://purl.uniprot.org/citations/10995765http://purl.uniprot.org/core/author"Howell P.L."xsd:string
http://purl.uniprot.org/citations/10995765http://purl.uniprot.org/core/author"Moremen K.W."xsd:string
http://purl.uniprot.org/citations/10995765http://purl.uniprot.org/core/author"Moremen K.W."xsd:string
http://purl.uniprot.org/citations/10995765http://purl.uniprot.org/core/author"Vallee F."xsd:string
http://purl.uniprot.org/citations/10995765http://purl.uniprot.org/core/author"Vallee F."xsd:string
http://purl.uniprot.org/citations/10995765http://purl.uniprot.org/core/author"Karaveg K."xsd:string
http://purl.uniprot.org/citations/10995765http://purl.uniprot.org/core/author"Karaveg K."xsd:string
http://purl.uniprot.org/citations/10995765http://purl.uniprot.org/core/author"Herscovics A."xsd:string
http://purl.uniprot.org/citations/10995765http://purl.uniprot.org/core/author"Herscovics A."xsd:string
http://purl.uniprot.org/citations/10995765http://purl.uniprot.org/core/date"2000"xsd:gYear
http://purl.uniprot.org/citations/10995765http://purl.uniprot.org/core/date"2000"xsd:gYear
http://purl.uniprot.org/citations/10995765http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/10995765http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/10995765http://purl.uniprot.org/core/pages"41287-41298"xsd:string
http://purl.uniprot.org/citations/10995765http://purl.uniprot.org/core/pages"41287-41298"xsd:string
http://purl.uniprot.org/citations/10995765http://purl.uniprot.org/core/title"Structural basis for catalysis and inhibition of N-glycan processing class I alpha 1,2-mannosidases."xsd:string
http://purl.uniprot.org/citations/10995765http://purl.uniprot.org/core/title"Structural basis for catalysis and inhibition of N-glycan processing class I alpha 1,2-mannosidases."xsd:string
http://purl.uniprot.org/citations/10995765http://purl.uniprot.org/core/volume"275"xsd:string
http://purl.uniprot.org/citations/10995765http://purl.uniprot.org/core/volume"275"xsd:string