PMID:9192616
| Citation |
Bogyo, M, McMaster, JS, Gaczynska, M, Tortorella, D, Goldberg, AL and Ploegh, H (1997) Covalent modification of the active site threonine of proteasomal beta subunits and the Escherichia coli homolog HslV by a new class of inhibitors. Proc. Natl. Acad. Sci. U.S.A. 94:6629-34 |
|---|---|
| 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 a 125I-labeled nitrophenol derivative (125I-NIP-L3VS) covalently modify the active site threonine of the catalytic beta subunits of the proteasome. Modification of Thermoplasma proteasomes demonstrates the requirement for a hydroxyl amino acid (threonine, serine) as nucleophile at the beta subunit's NH2 terminus. 125I-NIP-L3VS covalently modifies the HslV subunit of the Escherichia coli protease complex HslV/HslU, a reaction that requires ATP, and supports a catalytic mechanism shared with that of the eukaryotic proteasome. |
| Links | |
| Keywords |
ATP-Dependent Proteases; Adenosine Triphosphatases/chemistry; Adenosine Triphosphate/metabolism; Cysteine Endopeptidases/chemistry; Cysteine Endopeptidases/drug effects; Cysteine Endopeptidases/metabolism; Endopeptidases/chemistry; Enzyme Inhibitors/pharmacology; Escherichia coli/enzymology; Heat-Shock Proteins; Multienzyme Complexes/chemistry; Multienzyme Complexes/drug effects; Multienzyme Complexes/metabolism; Oligopeptides/pharmacology; Proteasome Endopeptidase Complex; Serine Endopeptidases; Sulfones/pharmacology; Thermoplasma/enzymology; Threonine/chemistry; Threonine/metabolism |
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