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PDBsum entry 5f84
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Transferase/hydrolase
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PDB id
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5f84
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References listed in PDB file
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Key reference
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Title
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Structural analysis of notch-Regulating rumi reveals basis for pathogenic mutations.
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Authors
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H.Yu,
H.Takeuchi,
M.Takeuchi,
Q.Liu,
J.Kantharia,
R.S.Haltiwanger,
H.Li.
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Ref.
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Nat Chem Biol, 2016,
12,
735-740.
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PubMed id
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Abstract
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Rumi O-glucosylates the EGF repeats of a growing list of proteins essential in
metazoan development, including Notch. Rumi is essential for Notch signaling,
and Rumi dysregulation is linked to several human diseases. Despite Rumi's
critical roles, it is unknown how Rumi glucosylates a serine of many but not all
EGF repeats. Here we report crystal structures of Drosophila Rumi as binary and
ternary complexes with a folded EGF repeat and/or donor substrates. These
structures provide insights into the catalytic mechanism and show that Rumi
recognizes structural signatures of the EGF motif, the U-shaped consensus
sequence, C-X-S-X-(P/A)-C and a conserved hydrophobic region. We found that five
Rumi mutations identified in cancers and Dowling-Degos disease are clustered
around the enzyme active site and adversely affect its activity. Our study
suggests that loss of Rumi activity may underlie these diseases, and the
mechanistic insights may facilitate the development of modulators of Notch
signaling.
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