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Titolo:
Cathepsins X and B display distinct activity profiles that can be exploited for inhibitor design
Autore:
Menard, R; Therrien, C; Lachance, P; Sulea, T; Qi, HT; Alvarez-Hernandez, A; Roush, WR;
Indirizzi:
Natl Res Council Canada, Biotechnol Res Inst, Montreal, PQ H4P 2R2, CanadaNatl Res Council Canada Montreal PQ Canada H4P 2R2 al, PQ H4P 2R2, Canada Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA Univ Michigan Ann ArborMI USA 48109 , Dept Chem, Ann Arbor, MI 48109 USA
Titolo Testata:
BIOLOGICAL CHEMISTRY
fascicolo: 5, volume: 382, anno: 2001,
pagine: 839 - 845
SICI:
1431-6730(200105)382:5<839:CXABDD>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
CYSTEINE PROTEASE; CRYSTAL-STRUCTURE; PROCATHEPSIN-B; PAPAIN FAMILY; PROTEINASES; PROPEPTIDE; RESOLUTION; PROREGION; ANALOGS;
Keywords:
carboxypeptidase; cathepsin B; cathepsin X; cysteine protease; inhibitor; specificity;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
21
Recensione:
Indirizzi per estratti:
Indirizzo: Menard, R Natl Res Council Canada, Biotechnol Res Inst, 6100 Royalmount Ave, Montreal, PQ H4P 2R2, Canada Natl Res Council Canada 6100 Royalmount AveMontreal PQ Canada H4P 2R2
Citazione:
R. Menard et al., "Cathepsins X and B display distinct activity profiles that can be exploited for inhibitor design", BIOL CHEM, 382(5), 2001, pp. 839-845

Abstract

The carboxypeptidase and endopeptidase activities of cathepsins X and B, as well as their inhibition by E-64 derivatives, have been investigated in detail and compared. The results clearly demonstrate that cathepsins X and Bdo not share similar activity profiles against substrates and inhibitors. Using quenched fluorogenic substrates, we show that cathepsin X preferentially cleaves substrates through a monopeptidyl carboxypeptidase pathway, while cathepsin B displays a preference for the dipeptidyl pathway. The preference for one or the other pathway is about the same for both enzymes, i. e.approximately 2 orders of magnitude. Cleavage of a C-terminal dipeptide ofa substrate by cathepsin X can be observed under conditions that preclude efficient monopeptidyl carboxypeptidase activity. In addition, an inhibitordesigned to exploit the unique structural features responsible for the carboxypeptidase activity of cathepsin X has been synthesized and tested against cathepsins X, B and L. Although of moderate potency, this E-64 derivative is the first reported example of a cathepsin X-specific inhibitor. By comparison, CA074 was found to inactivate cathepsin B at least 34 000-fold more efficiently than cathepsin X.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/07/20 alle ore 01:25:24