期刊
NATURE
卷 469, 期 7331, 页码 564-U168出版社
NATURE PORTFOLIO
DOI: 10.1038/nature09638
关键词
-
资金
- US National Institutes of Health
- US National Science Foundation
- Harvard Biomedical Accelerator Fund
The essential mammalian enzyme O-linked beta-N-acetylglucosamine transferase (O-GlcNAc transferase, here OGT) couples metabolic status to the regulation of a wide variety of cellular signalling pathways by acting as a nutrient sensor(1). OGT catalyses the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine (UDP-GlcNAc) to serines and threonines of cytoplasmic, nuclear and mitochondrial proteins(2,3), including numerous transcription factors(4), tumour suppressors, kinases(5), phosphatases(1) and histone-modifying proteins(6). Aberrant glycosylation by OGT has been linked to insulin resistance(7), diabetic complications(8), cancer(9) and neurodegenerative diseases including Alzheimer's(10). Despite the importance of OGT, the details of how it recognizes and glycosylates its protein substrates are largely unknown. We report here two crystal structures of human OGT, as a binary complex with UDP (2.8 angstrom resolution) and as a ternary complex with UDP and a peptide substrate (1.95 angstrom). The structures provide clues to the enzyme mechanism, show how OGT recognizes target peptide sequences, and reveal the fold of the unique domain between the two halves of the catalytic region. This information will accelerate the rational design of biological experiments to investigate OGT's functions; it will also help the design of inhibitors for use as cellular probes and help to assess its potential as a therapeutic target.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据