HCF-1 is cleaved in the active site of O-GlcNAc transferase.

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Version: Author's accepted manuscript
Serval ID
serval:BIB_0C03172DF49E
Type
Article: article from journal or magazin.
Collection
Publications
Title
HCF-1 is cleaved in the active site of O-GlcNAc transferase.
Journal
Science
Author(s)
Lazarus M.B., Jiang J., Kapuria V., Bhuiyan T., Janetzko J., Zandberg W.F., Vocadlo D.J., Herr W., Walker S.
ISSN
1095-9203 (Electronic)
ISSN-L
0036-8075
Publication state
Published
Issued date
2013
Peer-reviewed
Oui
Volume
342
Number
6163
Pages
1235-1239
Language
english
Abstract
Host cell factor-1 (HCF-1), a transcriptional co-regulator of human cell-cycle progression, undergoes proteolytic maturation in which any of six repeated sequences is cleaved by the nutrient-responsive glycosyltransferase, O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT). We report that the tetratricopeptide-repeat domain of O-GlcNAc transferase binds the carboxyl-terminal portion of an HCF-1 proteolytic repeat such that the cleavage region lies in the glycosyltransferase active site above uridine diphosphate-GlcNAc. The conformation is similar to that of a glycosylation-competent peptide substrate. Cleavage occurs between cysteine and glutamate residues and results in a pyroglutamate product. Conversion of the cleavage site glutamate into serine converts an HCF-1 proteolytic repeat into a glycosylation substrate. Thus, protein glycosylation and HCF-1 cleavage occur in the same active site.
Keywords
Amino Acid Motifs, Amino Acid Substitution, Catalytic Domain, Crystallography, X-Ray, Glycosylation, Host Cell Factor C1/chemistry, Host Cell Factor C1/metabolism, Humans, Hydrogen Bonding, Models, Molecular, N-Acetylglucosaminyltransferases/chemistry, N-Acetylglucosaminyltransferases/metabolism, Protein Conformation, Protein Structure, Tertiary, Proteolysis, Pyrrolidonecarboxylic Acid/metabolism, Recombinant Fusion Proteins/chemistry, Recombinant Fusion Proteins/metabolism, Uridine Diphosphate N-Acetylglucosamine/chemistry, Uridine Diphosphate N-Acetylglucosamine/metabolism
Pubmed
Web of science
Create date
26/12/2013 18:48
Last modification date
20/08/2019 12:33
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