Human α-L-iduronidase uses its own N-glycan as a substrate-binding and catalytic module.
Proc Natl Acad Sci U S A
; 110(36): 14628-33, 2013 Sep 03.
Article
em En
| MEDLINE
| ID: mdl-23959878
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 α-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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polissacarídeos
/
Modelos Moleculares
/
Iduronidase
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article