Abstract
The catalytic mechanism of the 20 S proteasome from the archaebacterium Thermoplasma acidophilum has been analyzed by site-directed mutagenesis of the β subunit and by inhibitor studies. Deletion of the amino-terminal threonine or its mutation to alanine led to inactivation of the enzyme. Mutation of the residue to serine led to a fully active enzyme, which was over ten times more sensitive to the serine protease inhibitor 3,4-dichloroisocoumarin. In combination with the crystal structure of a proteasome-inhibitor complex, the data show that the nucleophilic attack is mediated by the amino-terminal threonine of processed β subunits. The conservation pattern of this residue in eukaryotic sequences suggests that at least three of the seven eukaryotic β-type subunit branches should be proteolytically inactive.
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Dates
Type | When |
---|---|
Created | 18 years, 10 months ago (Oct. 27, 2006, 2:19 p.m.) |
Deposited | 1 year, 7 months ago (Jan. 14, 2024, 11:45 p.m.) |
Indexed | 3 months, 1 week ago (May 22, 2025, 5:48 a.m.) |
Issued | 30 years, 4 months ago (April 28, 1995) |
Published | 30 years, 4 months ago (April 28, 1995) |
Published Print | 30 years, 4 months ago (April 28, 1995) |
@article{Seem_ller_1995, title={Proteasome from Thermoplasma acidophilum : a Threonine Protease}, volume={268}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.7725107}, DOI={10.1126/science.7725107}, number={5210}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Seemüller, Erika and Lupas, Andrei and Stock, Daniela and Löwe, Jan and Huber, Robert and Baumeister, Wolfgang}, year={1995}, month=apr, pages={579–582} }