Human alpha-L-iduronidase uses its own N-glycan as a substrate-binding and catalytic module.
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Maita N, Tsukimura T, Taniguchi T, Saito S, Ohno K, Taniguchi H, Sakuraba H
Human alpha-L-iduronidase uses its own N-glycan as a substrate-binding and catalytic module.
Proc Natl Acad Sci U S A. 2013 Sep 3;110(36):14628-33. doi: 10.1073/pnas.1306939110. Epub 2013 Aug 19.
- PubMed ID
- 23959878 [ View in PubMed]
- Abstract
N-glycosylation is a major posttranslational modification that endows proteins with various functions. It is established that N-glycans are essential for the correct folding and stability of some enzymes; however, the actual effects of N-glycans on their activities are poorly understood. Here, we show that human alpha-l-iduronidase (hIDUA), of which a dysfunction causes accumulation of dermatan/heparan sulfate leading to mucopolysaccharidosis type I, uses its own N-glycan as a substrate binding and catalytic module. Structural analysis revealed that the mannose residue of the N-glycan attached to N372 constituted a part of the substrate-binding pocket and interacted directly with a substrate. A deglycosylation study showed that enzyme activity was highly correlated with the N-glycan attached to N372. The kinetics of native and deglycosylated hIDUA suggested that the N-glycan is also involved in catalytic processes. Our study demonstrates a previously unrecognized function of N-glycans.