@article { ISI:000183957900020,
	title = {Family 39 alpha-L-iduronidases and beta-D-xylosidases react through similar glycosyl-enzyme intermediates: Identification of the human iduronidase nucleophile},
	journal = {BIOCHEMISTRY},
	volume = {42},
	number = {26},
	year = {2003},
	month = {JUL 8},
	pages = {8054-8065},
	abstract = {The 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 at. (1998) Biochem. J. 335, 449-455]; thus, a common mechanism involving a covalent glycosyl-enzyme intermediate that adopts the rather uncommon B-2,B-5 conformation is predicted.},
	issn = {0006-2960},
	doi = {10.1021/bi034293v},
	author = {Nieman, CE and Wong, AW and He, SM and Clarke, L and Hopwood, JJ and Withers, SG}
}
