Abstract
O-GlcNAc hydrolase (OGA) catalyzes removal of βα-linked N-acetyl-D-glucosamine from serine and threonine residues. We report crystal structures of Homo sapiens OGA catalytic domain in apo and inhibited states, revealing a flexible dimer that displays three unique conformations and is characterized by subdomain α-helix swapping. These results identify new structural features of the substrate-binding groove adjacent to the catalytic site and open new opportunities for structural, mechanistic and drug discovery activities.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Acetylglucosamine / metabolism
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Binding Sites
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Calorimetry
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Catalytic Domain
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Crystallography, X-Ray
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Enzyme Activation / drug effects
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Enzyme Inhibitors / pharmacology
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Humans
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Models, Biological*
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Protein Structure, Tertiary
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Substrate Specificity
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beta-N-Acetylhexosaminidases / chemistry*
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beta-N-Acetylhexosaminidases / metabolism*
Substances
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Enzyme Inhibitors
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hexosaminidase C
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beta-N-Acetylhexosaminidases
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Acetylglucosamine