The cancer-associated glycosyltransferase GnT-V (MGAT5) recognizes the N-glycan core via residues outside its catalytic pocket.
MGAT5
N-acetylglucosaminyltransferase-V
asparagine-linked glycans
cancer metastasis
glycosylation
glycosyltransferase
Journal
FEBS letters
ISSN: 1873-3468
Titre abrégé: FEBS Lett
Pays: England
ID NLM: 0155157
Informations de publication
Date de publication:
17 Nov 2023
17 Nov 2023
Historique:
revised:
21
11
2023
received:
23
10
2023
accepted:
03
11
2023
pubmed:
17
11
2023
medline:
17
11
2023
entrez:
17
11
2023
Statut:
aheadofprint
Résumé
N-acetylglucosaminyltransferase-V (GnT-V or MGAT5) is a glycosyltransferase involved in cancer metastasis that creates the β1,6-branch on N-glycans of target proteins such as cell adhesion molecules and cell surface receptors. The 3D structure of GnT-V and its catalytic site, which are critical for the interaction with the N-glycan terminal, have already been revealed. However, it remains unclear how GnT-V recognizes the core part of N-glycan or the polypeptide part of the acceptor. Using molecular dynamics simulations and biochemical experiments, we found that several residues outside the catalytic pocket are likely involved in the recognition of the core part of N-glycan. Furthermore, our simulation suggested that UDP binding affects the orientation of the acceptor due to the conformational change at the Manα1,6-Man linkage. These findings provide new insights into how GnT-V recognizes its glycoprotein substrates.
Identifiants
pubmed: 37974463
doi: 10.1002/1873-3468.14775
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Japan Agency for Medical Research and Development
ID : JP22gm1410011
Organisme : Japan Science and Technology Agency
ID : 18070267
Organisme : Japan Science and Technology Agency
ID : 21468911
Organisme : Mizutani Foundation for Glycoscience
Organisme : Naito Foundation
Informations de copyright
© 2023 Federation of European Biochemical Societies.
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