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PDBsum entry 3v6e
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Hydrolase/signaling protein
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PDB id
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3v6e
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References listed in PDB file
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Key reference
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Title
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A strategy for modulation of enzymes in the ubiquitin system.
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Authors
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A.Ernst,
G.Avvakumov,
J.Tong,
Y.Fan,
Y.Zhao,
P.Alberts,
A.Persaud,
J.R.Walker,
A.M.Neculai,
D.Neculai,
A.Vorobyov,
P.Garg,
L.Beatty,
P.K.Chan,
Y.C.Juang,
M.C.Landry,
C.Yeh,
E.Zeqiraj,
K.Karamboulas,
A.Allali-Hassani,
M.Vedadi,
M.Tyers,
J.Moffat,
F.Sicheri,
L.Pelletier,
D.Durocher,
B.Raught,
D.Rotin,
J.Yang,
M.F.Moran,
S.Dhe-Paganon,
S.S.Sidhu.
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Ref.
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Science, 2013,
339,
590-595.
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PubMed id
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Abstract
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The ubiquitin system regulates virtually all aspects of cellular function. We
report a method to target the myriad enzymes that govern ubiquitination of
protein substrates. We used massively diverse combinatorial libraries of
ubiquitin variants to develop inhibitors of four deubiquitinases (DUBs) and
analyzed the DUB-inhibitor complexes with crystallography. We extended the
selection strategy to the ubiquitin conjugating (E2) and ubiquitin ligase (E3)
enzymes and found that ubiquitin variants can also enhance enzyme activity.
Last, we showed that ubiquitin variants can bind selectively to
ubiquitin-binding domains. Ubiquitin variants exhibit selective function in
cells and thus enable orthogonal modulation of specific enzymatic steps in the
ubiquitin system.
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