How the glycosyltransferase OGT catalyzes amide bond cleavage.
The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT), known for modulating the functions of nuclear and cytoplasmic proteins through serine and threonine glycosylation, was unexpectedly implicated in the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1). Here we show that HCF-1 cleavage occurs via glycosylation of a glutamate side chain followed by on-enzyme formation of an internal pyroglutamate, which undergoes spontaneous backbone hydrolysis.
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.|Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
John
J
Janetzko
Small Molecule Mass Spectrometry, Division of Science, Harvard University, Cambridge, Massachusetts, USA.
Sunia A
SA
Trauger
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.|Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
Michael B
MB
Lazarus
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
Suzanne
S
Walker
D000577:Amides / Q000737:chemistry* / Q000378:metabolism*; D055162:Biocatalysis; D051863:Host Cell Factor C1 / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*
D000577:Amides; C497692:HCFC1 protein, human; D051863:Host Cell Factor C1; D017351:N-Acetylglucosaminyltransferases