Crystal Structure of the Mannose-6-Phosphate Uncovering Enzyme.
M6P
N-acetylglucosamine
NAGPA
glycosidase
mannose-6-phosphate
Journal
Structure (London, England : 1993)
ISSN: 1878-4186
Titre abrégé: Structure
Pays: United States
ID NLM: 101087697
Informations de publication
Date de publication:
07 04 2020
07 04 2020
Historique:
received:
23
12
2019
revised:
02
02
2020
accepted:
11
02
2020
pubmed:
29
2
2020
medline:
17
4
2021
entrez:
29
2
2020
Statut:
ppublish
Résumé
Most lysosomal hydrolytic enzymes reach their destination via the mannose-6-phosphate (M6P) pathway. The enzyme N-acetylglucosamine-1-phosphodiester α-N-acetylglucosaminidase (NAGPA, or "uncovering enzyme") catalyzes the second step in the M6P tag formation, namely the removal of the masking N-acetylglucosamine (GlcNAc) portion. Defects in this protein are associated with non-syndromic stuttering. To gain a better understanding of the function and regulation of this enzyme, we determined its crystal structure. The propeptide binds in a groove on the globular catalytic domain, blocking active site access. High-affinity substrate binding is enabled by a conformational switch in an active site loop. The protein recognizes the GlcNAc and phosphate portions of its substrate, but not the mannose moiety of the glycan. Based on enzymatic and
Identifiants
pubmed: 32109365
pii: S0969-2126(20)30042-3
doi: 10.1016/j.str.2020.02.001
pii:
doi:
Substances chimiques
Mannosephosphates
0
mannose-6-phosphate
3672-15-9
Phosphoric Diester Hydrolases
EC 3.1.4.-
N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase
EC 3.1.4.45
Acetylglucosamine
V956696549
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
426-436.e3Subventions
Organisme : CIHR
ID : MOP-133535
Pays : Canada
Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.