Title : Human α
-L-iduronidase uses
its own N-glycan as a substrate-binding and catalytic module
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