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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2001-3-12
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pubmed:abstractText |
The chymotrypsin-like (CT-L) activity of the proteasome is downregulated by substrates of the peptidyl-glutamyl peptide hydrolyzing (PGPH) activity. To investigate the nature of such interactions, we synthesized selective alpha',beta'-epoxyketone inhibitors of the PGPH activity. In cellular proliferation and protein degradation assays, these inhibitors revealed that selective PGPH inhibition was insufficient to inhibit protein degradation, indicating that the CT-L and PGPH sites function independently. We also demonstrated that CT-L inhibition by a PGPH substrate does not require the occupancy of the PGPH site or hydrolysis of the PGPH substrate. Thus, these results support a model in which a substrate of one subunit regulates the activity of another via binding to a noncatalytic site(s) rather than through binding to an active site.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Chymotrypsin,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Epoxy Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Ketones,
http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/Protease Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Subunits,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/dihydroeponemycin,
http://linkedlifedata.com/resource/pubmed/chemical/peptidylglutamylpeptide hydrolase
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1097-2765
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
7
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
411-20
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pubmed:dateRevised |
2009-10-1
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pubmed:meshHeading |
pubmed-meshheading:11239469-Allosteric Regulation,
pubmed-meshheading:11239469-Animals,
pubmed-meshheading:11239469-Binding Sites,
pubmed-meshheading:11239469-Cattle,
pubmed-meshheading:11239469-Cell Division,
pubmed-meshheading:11239469-Cells, Cultured,
pubmed-meshheading:11239469-Chymotrypsin,
pubmed-meshheading:11239469-Cysteine Endopeptidases,
pubmed-meshheading:11239469-Endopeptidases,
pubmed-meshheading:11239469-Epoxy Compounds,
pubmed-meshheading:11239469-Humans,
pubmed-meshheading:11239469-Hydrolysis,
pubmed-meshheading:11239469-Ketones,
pubmed-meshheading:11239469-Kinetics,
pubmed-meshheading:11239469-Models, Biological,
pubmed-meshheading:11239469-Multienzyme Complexes,
pubmed-meshheading:11239469-Protease Inhibitors,
pubmed-meshheading:11239469-Proteasome Endopeptidase Complex,
pubmed-meshheading:11239469-Protein Subunits,
pubmed-meshheading:11239469-Recombinant Fusion Proteins,
pubmed-meshheading:11239469-Serine,
pubmed-meshheading:11239469-Substrate Specificity,
pubmed-meshheading:11239469-Transfection
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pubmed:year |
2001
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pubmed:articleTitle |
Lack of proteasome active site allostery as revealed by subunit-specific inhibitors.
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pubmed:affiliation |
Department of Molecular, Cellular, and Developmental Biology, New Haven, CT 06520, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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