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PDBsum entry 4r18
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Hydrolase/hydrolase inhibitor
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PDB id
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4r18
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Contents |
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250 a.a.
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244 a.a.
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240 a.a.
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235 a.a.
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231 a.a.
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243 a.a.
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241 a.a.
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226 a.a.
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204 a.a.
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195 a.a.
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211 a.a.
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222 a.a.
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233 a.a.
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196 a.a.
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References listed in PDB file
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Key reference
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Title
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Selective inhibition of the immunoproteasome by ligand-Induced crosslinking of the active site.
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Authors
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C.Dubiella,
H.Cui,
M.Gersch,
A.J.Brouwer,
S.A.Sieber,
A.Krüger,
R.M.Liskamp,
M.Groll.
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Ref.
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Angew Chem Int Ed Engl, 2014,
53,
11969-11973.
[DOI no: ]
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PubMed id
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Abstract
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The concept of proteasome inhibition ranks among the latest achievements in the
treatment of blood cancer and represents a promising strategy for modulating
autoimmune diseases. In this study, we describe peptidic sulfonyl fluoride
inhibitors that selectively block the catalytic β5 subunit of the
immunoproteasome by inducing only marginal cytotoxic effects. Structural and
mass spectrometric analyses revealed a novel reaction mechanism involving
polarity inversion and irreversible crosslinking of the proteasomal active site.
We thus identified the sulfonyl fluoride headgroup for the development and
optimization of immunoproteasome selective compounds and their possible
application in autoimmune disorders.
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