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PDBsum entry 2dyh
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Transcription
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PDB id
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2dyh
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References listed in PDB file
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Key reference
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Title
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Different electrostatic potentials define etge and dlg motifs as hinge and latch in oxidative stress response.
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Authors
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K.I.Tong,
B.Padmanabhan,
A.Kobayashi,
C.Shang,
Y.Hirotsu,
S.Yokoyama,
M.Yamamoto.
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Ref.
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Mol Cell Biol, 2007,
27,
7511-7521.
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PubMed id
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Abstract
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Nrf2 is the regulator of the oxidative/electrophilic stress response. Its
turnover is maintained by Keap1-mediated proteasomal degradation via a two-site
substrate recognition mechanism in which two Nrf2-Keap1 binding sites form a
hinge and latch. The E3 ligase adaptor Keap1 recognizes Nrf2 through its
conserved ETGE and DLG motifs. In this study, we examined how the ETGE and DLG
motifs bind to Keap1 in a very similar fashion but with different binding
affinities by comparing the crystal complex of a Keap1-DC domain-DLG peptide
with that of a Keap1-DC domain-ETGE peptide. We found that these two motifs
interact with the same basic surface of either Keap1-DC domain of the Keap1
homodimer. The DLG motif works to correctly position the lysines within the Nrf2
Neh2 domain for efficient ubiquitination. Together with the results from
calorimetric and functional studies, we conclude that different electrostatic
potentials primarily define the ETGE and DLG motifs as a hinge and latch that
senses the oxidative/electrophilic stress.
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