3W82

Human alpha-L-iduronidase in complex with iduronic acid

Summary for 3W82

• Entry DOI: 10.2210/pdb3w82/pdb
• Related: 3W81
• Descriptor: Alpha-L-iduronidase, L(+)-TARTARIC ACID, PHOSPHITE ION, ... (12 entities in total)
• Functional Keywords: tim barrel, glycosyl hydrolase, glycosylation, lysosome, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Lysosome: P35475
• Total number of polymer chains: 2
• Total formula weight: 146064.51

Authors

Maita, N.,Tsukimura, T.,Taniguchi, T.,Saito, S.,Ohno, K.,Taniguchi, H.,Sakuraba, H. (deposition date: 2013-03-11, release date: 2013-08-21, Last modification date: 2024-10-30)

Primary citation

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.USA, 110:14628-14633, 2013

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 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.

PubMed: 23959878
DOI: 10.1073/pnas.1306939110

Experimental method

X-RAY DIFFRACTION (2.76 Å)