Editors' ChoiceBiochemistry

Dual-Duty Active Site

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Sci. Signal.  10 Dec 2013:
Vol. 6, Issue 305, pp. ec301
DOI: 10.1126/scisignal.2004972

O-linked N-acetylglucosamine transferase (OGT) catalyzes the addition of N-acetylglucosamine (GlcNac) to serine or threonine residues, influencing the localization and function of proteins. Because its activity is sensitive to the nutrient uridine diphosphate (UDP)–GlcNac, OGT has been proposed to regulate cellular responses to nutrient status. Recently, OGT in the presence of UDP-GlcNac was shown to cleave host cell factor–1 (HCF-1), a transcriptional coregulator of human cell-cycle progression. This cleavage is required for HCF-1 maturation. Through a combination of structural, biochemical, and mutagenesis studies, Lazarus et al. show that both cleavage and glycosylation of HCF-1 occur in the OGT active site. Cleavage occurs between cysteine and glutamine and converts the glutamine into a serine which can then be glycosylated.

M. B. Lazarus, J. Jiang, V. Kapuria, T. Bhuiyan, J. Janetzko, W. F. Zandberg, D. J. Vocadlo, W. Herr, S. Walker, HCF-1 is cleaved in the active site of O-GlcNAc transferase. Science 342, 1235–1239 (2013). [Abstract] [Full Text]

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