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PDBsum entry 3pe3
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References listed in PDB file
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Key reference
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Title
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Structure of human o-Glcnac transferase and its complex with a peptide substrate.
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Authors
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M.B.Lazarus,
Y.Nam,
J.Jiang,
P.Sliz,
S.Walker.
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Ref.
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Nature, 2011,
469,
564-567.
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PubMed id
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Abstract
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The essential mammalian enzyme O-linked β-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. OGT
catalyses the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine
(UDP-GlcNAc) to serines and threonines of cytoplasmic, nuclear and mitochondrial
proteins, including numerous transcription factors, tumour suppressors, kinases,
phosphatases and histone-modifying proteins. Aberrant glycosylation by OGT has
been linked to insulin resistance, diabetic complications, cancer and
neurodegenerative diseases including Alzheimer's. 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 Å resolution) and as a ternary complex with UDP and a
peptide substrate (1.95 Å). 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.
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