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Structural and functional insight into human O-GlcNAcase.

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.

SUBMITTER: Roth C

PROVIDER: S-EPMC5438047 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Structural and functional insight into human O-GlcNAcase.

Roth Christian C Chan Sherry S Offen Wendy A WA Hemsworth Glyn R GR Willems Lianne I LI King Dustin T DT Varghese Vimal V Britton Robert R Vocadlo David J DJ Davies Gideon J GJ

Nature chemical biology 20170327 6

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 t ...[more]

PMID: 28346405

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