DOI: 10.1073/pnas.94.13.6629. Covalent modification of the active site threonine of proteasomal β subunits and the<i>Escherichia coli</i>homolog HslV by a new class of inhibitors

Covalent modification of the active site threonine of proteasomal β subunits and theEscherichia colihomolog HslV by a new class of inhibitors

10.1073/pnas.94.13.6629

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The proteasome is a multicatalytic protease complex that plays a key role in diverse cellular functions. The peptide vinyl sulfone, carboxybenzyl-leucyl-leucyl-leucine vinyl sulfone (Z-L3VS) covalently inhibits the trypsin-like, chymotrypsin-like and, unlike lactacystin, also the peptidylglutamyl peptidase activity in isolated proteasomes, and blocks their function in living cells. Although described as a class of mechanism-based inhibitors for cysteine proteases, the peptide vinyl sulfone Z-L3VS and a125I-labeled nitrophenol derivative (125I-NIP-L3VS) covalently modify the active site threonine of the catalytic β subunits of the proteasome. Modification of Thermoplasma proteasomes demonstrates the requirement for a hydroxyl amino acid (threonine, serine) as nucleophile at the β subunit’s NH2terminus.125I-NIP-L3VS covalently modifies the HslV subunit of theEscherichia coliprotease complex HslV/HslU, a reaction that requires ATP, and supports a catalytic mechanism shared with that of the eukaryotic proteasome.

Bibliography

Bogyo, M., McMaster, J. S., Gaczynska, M., Tortorella, D., Goldberg, A. L., & Ploegh, H. (1997). Covalent modification of the active site threonine of proteasomal Î² subunits and theEscherichia colihomolog HslV by a new class ofâinhibitors. Proceedings of the National Academy of Sciences, 94(13), 6629â6634.

Authors 6

Matthew Bogyo (first)
John S. McMaster (additional)
Maria Gaczynska (additional)
Domenico Tortorella (additional)
Alfred L. Goldberg (additional)
Hidde Ploegh (additional)

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Dates

Type	When
Created	23 years ago (July 26, 2002, 10:40 a.m.)
Deposited	1 year, 7 months ago (Jan. 4, 2024, 12:05 a.m.)
Indexed	3 weeks, 5 days ago (July 30, 2025, 11:04 a.m.)
Issued	28 years, 2 months ago (June 24, 1997)
Published	28 years, 2 months ago (June 24, 1997)
Published Online	28 years, 2 months ago (June 24, 1997)
Published Print	28 years, 2 months ago (June 24, 1997)

Funders 0

None

BibTeX

@article{Bogyo_1997, title={Covalent modification of the active site threonine of proteasomal β subunits and theEscherichia colihomolog HslV by a new class of inhibitors}, volume={94}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.94.13.6629}, DOI={10.1073/pnas.94.13.6629}, number={13}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Bogyo, Matthew and McMaster, John S. and Gaczynska, Maria and Tortorella, Domenico and Goldberg, Alfred L. and Ploegh, Hidde}, year={1997}, month=jun, pages={6629–6634} }

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