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5lai

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Ligand-induced aziridine-formation at the yeast proteasomal subunit beta5 by sulfonate esters

Structural highlights

5lai is a 20 chain structure with sequence from Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.5Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PSA2_YEAST The proteasome degrades poly-ubiquitinated proteins in the cytoplasm and in the nucleus. It is essential for the regulated turnover of proteins and for the removal of misfolded proteins. The proteasome is a multicatalytic proteinase complex that is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. It has an ATP-dependent proteolytic activity.

Publication Abstract from PubMed

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.

Tunable Probes with Direct Fluorescence Signals for the Constitutive and Immunoproteasome.,Dubiella C, Cui H, Groll M Angew Chem Int Ed Engl. 2016 Oct 10;55(42):13330-13334. doi:, 10.1002/anie.201605753. PMID:27709817^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Dubiella C, Cui H, Groll M. Tunable Probes with Direct Fluorescence Signals for the Constitutive and Immunoproteasome. Angew Chem Int Ed Engl. 2016 Oct 10;55(42):13330-13334. doi:, 10.1002/anie.201605753. PMID:27709817 doi:http://dx.doi.org/10.1002/anie.201605753