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Titolo:
Evidence for the existence of a non-catalytic modifier site of peptide hydrolysis by the 20 S proteasome
Autore:
Schmidtke, G; Emch, S; Groettrup, M; Holzhutter, HG;
Indirizzi:
Kantonsspital St Gallen, Lab Forsch Abt, Res Dept, CH-9007 St Gallen, Switzerland Kantonsspital St Gallen St Gallen Switzerland CH-9007 allen, Switzerland Humboldt Univ, Fac Med Charite, Inst Biochem, D-10117 Berlin, Germany Humboldt Univ Berlin Germany D-10117 st Biochem, D-10117 Berlin, Germany
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 29, volume: 275, anno: 2000,
pagine: 22056 - 22063
SICI:
0021-9258(20000721)275:29<22056:EFTEOA>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
MAJOR HISTOCOMPATIBILITY COMPLEX; MULTICATALYTIC PROTEINASE COMPLEX; SENSITIVE NEUTRAL ENDOPEPTIDASE; I ANTIGEN PRESENTATION; RAT-LIVER; ACTIVE-SITES; LACTACYSTIN; INHIBITOR; ACIDOPHILUM; SPECIFICITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
33
Recensione:
Indirizzi per estratti:
Indirizzo: Groettrup, M Kantonsspital St Gallen, Lab Forsch Abt, Res Dept, Haus 09, CH-9007 St Gallen, Switzerland Kantonsspital St Gallen Haus 09 St Gallen Switzerland CH-9007
Citazione:
G. Schmidtke et al., "Evidence for the existence of a non-catalytic modifier site of peptide hydrolysis by the 20 S proteasome", J BIOL CHEM, 275(29), 2000, pp. 22056-22063

Abstract

The 20 S proteasome is an endoprotease complex that preferentially cleavespeptides C-terminal of hydrophobic, basic, and acidic residues. Recently, we showed that these specific activities, classified as chymotrypsin-like, trypsin-like, and peptidylglutamyl peptide-hydrolyzing (PGPH) activity, aredifferently affected by Ritonavir, an inhibitor of human immunodeficiency virus-1 protease, Ritonavir competitively inhibited the chymotrypsin-like activity, whereas the trypsin-like activity was enhanced. Here we demonstrate that the Ritonavir-mediated up-regulation of the trypsin-like activity isnot affected by specific active site inhibitors of the chymotrypsin-like and PG:PH activity. Moreover, we show that the mutual regulation of chymotrypsin-like and PGPH activities by their substrates as described previously by a "cyclical bite-chew" model is not affected by selective inhibitors of the respective active sites. These data challenge the bite-chew model and suggest that effecters of proteasome activity can act by binding to non-catalytic sites. Accordingly, we propose a kinetic "two-site modifier" model that assumes that the substrate (or effector) may bind to an active site as well as to a second noncatalytic modifier site. This model appears to be valid as it describes the complex kinetic effects of Ritonavir very well. SinceRitonavir partially inhibits major histocompatibility complex class I restricted antigen presentation, the postulated modifier site may be required to coordinate the active centers of the proteasome for the production of class I peptide ligands.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 09:37:50