Structural characterization of the O-GlcNAc cycling enzymes: insights into substrate recognition and catalytic mechanisms.


Journal

Current opinion in structural biology
ISSN: 1879-033X
Titre abrégé: Curr Opin Struct Biol
Pays: England
ID NLM: 9107784

Informations de publication

Date de publication:
06 2019
Historique:
received: 23 08 2018
accepted: 05 12 2018
pubmed: 2 2 2019
medline: 9 6 2020
entrez: 2 2 2019
Statut: ppublish

Résumé

Dysregulation of nuclear and cytoplasmic O-linked β-N-acetylglucosamine (O-GlcNAc) cycling is implicated in a range of diseases including diabetes and cancer. This modification maintains cellular homeostasis by regulating several biological processes, such as cell signaling. This highly regulated cycle is governed by two sole essential enzymes, O-GlcNAc transferase and O-GlcNAcase that add O-GlcNAc and remove it from over a thousand substrates, respectively. Until recently, due to lack of structural information, the mechanism of substrate recognition has eluted researchers. Here, we review recent successes in structural characterization of these enzymes and how this information has illuminated key features essential for catalysis and substrate recognition. Additionally, we highlight recent studies which have used this information to expand our understanding of substrate specificity by each enzyme.

Identifiants

pubmed: 30708324
pii: S0959-440X(18)30099-X
doi: 10.1016/j.sbi.2018.12.003
pmc: PMC6656603
mid: NIHMS1516959
pii:
doi:

Substances chimiques

Transferases EC 2.-
Acetylglucosamine V956696549

Types de publication

Journal Article Research Support, N.I.H., Extramural Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

97-106

Subventions

Organisme : NIGMS NIH HHS
ID : R01 GM094263
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM121718
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM126300
Pays : United States

Informations de copyright

Copyright © 2018 Elsevier Ltd. All rights reserved.

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Auteurs

Cassandra M Joiner (CM)

Department of Microbiology, Harvard Medical School, 4 Blackfan Circle, Boston, MA 02115, United States.

Hao Li (H)

School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705, United States.

Jiaoyang Jiang (J)

School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705, United States. Electronic address: jjiang68@wisc.edu.

Suzanne Walker (S)

Department of Microbiology, Harvard Medical School, 4 Blackfan Circle, Boston, MA 02115, United States. Electronic address: suzanne_walker@hms.harvard.edu.

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