5LAI

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

Summary for 5LAI

• Entry DOI: 10.2210/pdb5lai/pdb
• Related: 4R17 5CZ4
• Descriptor: Proteasome subunit alpha type-2, Proteasome subunit beta type-4, Proteasome subunit beta type-5, ... (17 entities in total)
• Functional Keywords: proteasome, fluorescent probes, binding analysis, umpolung, crosslink, hydrolase
• Biological source: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast); More
• Cellular location: Cytoplasm: P23639 P22141 P30656 P23724 P30657 P38624 P23638 P40303 P32379 P40302 P21242 P21243 P25043 P25451
• Total number of polymer chains: 28
• Total formula weight: 731520.33

Authors

Groll, M.,Dubiella, C.,Cui, H. (deposition date: 2016-06-14, release date: 2017-04-26, Last modification date: 2024-01-10)

Primary citation

Dubiella, C.,Cui, H.,Groll, M.
Tunable Probes with Direct Fluorescence Signals for the Constitutive and Immunoproteasome.
Angew. Chem. Int. Ed. Engl., 55:13330-13334, 2016

PubMed Abstract: 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 pK 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.

PubMed: 27709817
DOI: 10.1002/anie.201605753

Experimental method

X-RAY DIFFRACTION (2.5 Å)