Mechanism of glucocerebrosidase activation and dysfunction in Gaucher disease unraveled by molecular dynamics and deep learning.
gene mutations
lysosomal storage disease
multiscale simulations
rare disease
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
12 03 2019
12 03 2019
Historique:
pubmed:
28
2
2019
medline:
7
5
2019
entrez:
28
2
2019
Statut:
ppublish
Résumé
The lysosomal enzyme glucocerebrosidase-1 (GCase) catalyzes the cleavage of a major glycolipid glucosylceramide into glucose and ceramide. The absence of fully functional GCase leads to the accumulation of its lipid substrates in lysosomes, causing Gaucher disease, an autosomal recessive disorder that displays profound genotype-phenotype nonconcordance. More than 250 disease-causing mutations in
Identifiants
pubmed: 30808805
pii: 1818411116
doi: 10.1073/pnas.1818411116
pmc: PMC6421449
doi:
Substances chimiques
Mutant Proteins
0
Saposins
0
Glucosylceramidase
EC 3.2.1.45
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
5086-5095Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR067066
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR065932
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG060917
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK113627
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG023176
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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