O-GlcNAc Peptide Epoxyketones Are Recognized by Mammalian Proteasomes
نویسندگان
چکیده
منابع مشابه
Bisubstrate UDP–peptide conjugates as human O-GlcNAc transferase inhibitors
Inhibitors of OGT (O-GlcNAc transferase) are valuable tools to study the cell biology of protein O-GlcNAcylation. We report OGT bisubstrate-linked inhibitors (goblins) in which the acceptor serine in the peptide VTPVSTA is covalently linked to UDP, eliminating the GlcNAc pyranoside ring. Goblin1 co-crystallizes with OGT, revealing an ordered C₃ linker and retained substrate-binding modes, and b...
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O-GlcNAcylation is a common posttranslational modification of nucleocytoplasmic proteins by β-N-acetylglucosamine (GlcNAc). The dynamic addition and removal of O-GlcNAc groups to and from proteins are catalyzed by O-linked N-acetylglucosamine transferase (O-GlcNAc transferase, OGT) and β-N-acetylglucosaminidase (O-GlcNAcase, OGA), respectively. O-GlcNAcylation often modulates protein phosphoryl...
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The mammalian O-GlcNAc hydrolase (OGA) removes O-GlcNAc from serine and threonine residues on intracellular glycoproteins. OGA activity is sensitive to N-acyl substitutions to O-GlcNAc, with alkyl diazirine-modified O-GlcNAc (O-GlcNDAz) being completely resistant to removal by OGA. Using homology modeling, we identified OGA residues proximal to the N-acyl position of O-GlcNAc substrate. Mutatio...
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ژورنال
عنوان ژورنال: Journal of the American Chemical Society
سال: 2009
ISSN: 0002-7863,1520-5126
DOI: 10.1021/ja901231w