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PDBsum entry 5lai
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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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Tunable probes with direct fluorescence signals for the constitutive and immunoproteasome.
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Authors
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C.Dubiella,
H.Cui,
M.Groll.
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Ref.
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Angew Chem Int Ed Engl, 2016,
55,
13330-13334.
[DOI no: ]
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PubMed id
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Abstract
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Electrophiles are commonly used for the inhibition of proteases. Notably,
inhibitors of the proteasome, a central determinant of cellular survival and a
target of several FDA-approved drugs, are mainly characterized by the reactivity
of their electrophilic head groups. We aimed to tune the inhibitory strength of
peptidic sulfonate esters by varying the leaving groups. Indeed, proteasome
inhibition correlated well with the pKa of the leaving group. The use of
fluorophores as leaving groups enabled us to design probes that release a
stoichiometric fluorescence signal upon reaction, thereby directly linking
proteasome inactivation to the readout. This principle could be applicable to
other sulfonyl fluoride based inhibitors and allows the design of sensitive
probes for enzymatic studies.
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