Structural and functional insight into human O-GlcNAcase

Christian Roth; Oi Yi Chan; Wendy Anne Offen; Glyn Robert Hemsworth; Lianne Irene Willems; Dustin T. King; Vimal Varghese; Robert Britton; David J. Vocadlo; Gideon John Davies

doi:10.1038/nchembio.2358

Structural and functional insight into human O-GlcNAcase

Christian Roth^*, Oi Yi Chan, Wendy Anne Offen, Glyn Robert Hemsworth, Lianne Irene Willems, Dustin T. King, Vimal Varghese, Robert Britton, David J. Vocadlo, Gideon John Davies

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

O-GlcNAc hydrolase (OGA) removes O-linked N-acetylglucosamine (O-GlcNAc) from a myriad of nucleocytoplasmic proteins. Through co-expression and assembly of OGA fragments, we determined the three-dimensional structure of human OGA, revealing an unusual helix-exchanged dimer that lays a structural foundation for an improved understanding of substrate recognition and regulation of OGA. Structures of OGA in complex with a series of inhibitors define a precise blueprint for the design of inhibitors that have clinical value.

Original language	English
Pages (from-to)	610-612
Number of pages	3
Journal	NATURE CHEMICAL BIOLOGY
Volume	13
Issue number	6
Early online date	27 Mar 2017
DOIs	https://doi.org/10.1038/nchembio.2358
Publication status	Published - 1 Jun 2017

Bibliographical note

© 2017, Nature America, Inc. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details.

Keywords

Acetylglucosamine/metabolism
Binding Sites
Enzyme Activation/drug effects
Enzyme Inhibitors/pharmacology
HEK293 Cells
Humans
Ligands
Models, Molecular
Protein Binding
Protein Isoforms/chemistry
Protein Structure, Tertiary
beta-N-Acetylhexosaminidases/chemistry

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10.1038/nchembio.2358

18460_2_merged_1489089300
© 2017, Nature America, Inc. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details.
Accepted author manuscript, 9.98 MBLicence: Unspecified

Cite this

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abstract = "O-GlcNAc hydrolase (OGA) removes O-linked N-acetylglucosamine (O-GlcNAc) from a myriad of nucleocytoplasmic proteins. Through co-expression and assembly of OGA fragments, we determined the three-dimensional structure of human OGA, revealing an unusual helix-exchanged dimer that lays a structural foundation for an improved understanding of substrate recognition and regulation of OGA. Structures of OGA in complex with a series of inhibitors define a precise blueprint for the design of inhibitors that have clinical value.",

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author = "Christian Roth and Chan, {Oi Yi} and Offen, {Wendy Anne} and Hemsworth, {Glyn Robert} and Willems, {Lianne Irene} and King, {Dustin T.} and Vimal Varghese and Robert Britton and Vocadlo, {David J.} and Davies, {Gideon John}",

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AU - Offen, Wendy Anne

AU - Hemsworth, Glyn Robert

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AU - King, Dustin T.

AU - Varghese, Vimal

AU - Britton, Robert

AU - Vocadlo, David J.

AU - Davies, Gideon John

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KW - Ligands

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KW - Protein Binding

KW - Protein Isoforms/chemistry

KW - Protein Structure, Tertiary

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Structural and functional insight into human O-GlcNAcase

Abstract

Bibliographical note

Keywords

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Other files and links

Gideon John Davies, FRS, FMedSci

Lianne Irene Willems

Structural and fragment approaches to the modulation of O-GlcNAc in cells

Cite this

Structural and functional insight into human O-GlcNAcase

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Profiles

Gideon John Davies, FRS, FMedSci

Lianne Irene Willems

Projects

Structural and fragment approaches to the modulation of O-GlcNAc in cells

Cite this