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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Acetylglucosamine / metabolism
-
Binding Sites
-
Enzyme Activation / drug effects
-
Enzyme Inhibitors / pharmacology
-
HEK293 Cells
-
Humans
-
Ligands
-
Models, Molecular*
-
Protein Binding
-
Protein Isoforms / chemistry
-
Protein Isoforms / genetics
-
Protein Structure, Tertiary
-
beta-N-Acetylhexosaminidases / chemistry*
-
beta-N-Acetylhexosaminidases / genetics
-
beta-N-Acetylhexosaminidases / metabolism
Substances
-
Enzyme Inhibitors
-
Ligands
-
Protein Isoforms
-
hexosaminidase C
-
beta-N-Acetylhexosaminidases
-
Acetylglucosamine