Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/7022
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dc.contributor.authorNieman, C.-
dc.contributor.authorWong, A.-
dc.contributor.authorHe, S.-
dc.contributor.authorClarke, L.-
dc.contributor.authorHopwood, J.-
dc.contributor.authorWithers, S.-
dc.date.issued2003-
dc.identifier.citationBiochemistry, 2003; 42(26):8054-8065-
dc.identifier.issn0006-2960-
dc.identifier.issn1520-4995-
dc.identifier.urihttp://hdl.handle.net/2440/7022-
dc.description.abstractThe inclusion of both beta-D-xylosidases and alpha-L-iduronidases within the same sequence-related family (family 39), despite the considerable difference in substrate structures and poor sequence conservation around the putative nucleophile, raises concerns about whether a common mechanism is followed by the two enzymes. A novel anchimeric assistance mechanism for iduronidases involving a lactone intermediate is one possibility. NMR analysis of the methanolysis reaction catalyzed by human alpha-L-iduronidase reveals that, as with the beta-D-xylosidases, alpha-L-iduronidase is a retaining glycosidase. Using two different mechanism-based inactivators, 5-fluoro-alpha-L-iduronyl fluoride and 2-deoxy-2-fluoro-alpha-L-iduronyl fluoride, the active site nucleophile in the human alpha-L-iduronidase was identified as Glu299 within the (295)IYNDEAD(301) sequence. The equivalent, though loosely predicted, glutamic acid was identified as the nucleophile in the family 39 beta-D-xylosidase from Bacillus sp. [Vocadlo, D., et al. (1998) Biochem. J. 335, 449-455]; thus, a common mechanism involving a covalent glycosyl-enzyme intermediate that adopts the rather uncommon (2,5)B conformation is predicted.-
dc.language.isoen-
dc.publisherAmer Chemical Soc-
dc.subjectHumans-
dc.subjectBacillus-
dc.subjectIduronic Acid-
dc.subjectIduronidase-
dc.subjectXylosidases-
dc.subjectGlutamic Acid-
dc.subjectPeptide Fragments-
dc.subjectBinding Sites-
dc.subjectAmino Acid Sequence-
dc.subjectCatalytic Domain-
dc.subjectConserved Sequence-
dc.subjectSequence Homology, Amino Acid-
dc.subjectKinetics-
dc.subjectStereoisomerism-
dc.subjectMolecular Sequence Data-
dc.subjectMass Spectrometry-
dc.titleFamily 39 a-L-iduronidases and b-D-xylosidases react through similar glycosyl-enzyme intermediates: Identification of the human iduronidase nucleophile-
dc.typeJournal article-
dc.identifier.doi10.1021/bi034293v-
pubs.publication-statusPublished-
Appears in Collections:Aurora harvest
Paediatrics publications

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