Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
SUBSTRATE-SPECIFICITY OF PROSTATE-SPECIFIC ANTIGEN (PSA)
Autore:
COOMBS GS; BERGSTROM RC; PELLEQUER JL; BAKER SI; NAVRE M; SMITH MM; TAINER JA; MADISON EL; COREY DR;
Indirizzi:
CORVAS INT,DEPT BIOL MOL,3030 SCI PK RD SAN DIEGO CA 92121 CORVAS INT,DEPT BIOL MOL SAN DIEGO CA 92121 UNIV TEXAS,SW MED CTR,DEPT PHARMACOL,HOWARD HUGHES MED INST DALLAS TX75235 UNIV TEXAS,SW MED CTR,DEPT BIOCHEM,HOWARD HUGHES MED INST DALLAS TX 75235 SCRIPPS CLIN,RES INST,DEPT MOL BIOL LA JOLLA CA 92037 AFFYMAX RES INST SANTA CLARA CA 95501
Titolo Testata:
Chemistry & biology
fascicolo: 9, volume: 5, anno: 1998,
pagine: 475 - 488
SICI:
1074-5521(1998)5:9<475:SOPA(>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN GLANDULAR KALLIKREIN; PLASMINOGEN-ACTIVATOR; CRYSTAL-STRUCTURE; SERINE-PROTEASE; BIOCHEMICAL CHARACTERISTICS; PROTEOLYTIC ACTIVITY; GAMMA-SEMINOPROTEIN; MOLECULAR-DYNAMICS; CATALYTIC DOMAIN; ANGIOTENSIN-II;
Keywords:
PROSTATE-SPECIFIC ANTIGEN; PROTEASE SPECIFICITY; SUBSITE OCCUPANCY; SUBSTRATE PHAGE DISPLAY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
60
Recensione:
Indirizzi per estratti:
Citazione:
G.S. Coombs et al., "SUBSTRATE-SPECIFICITY OF PROSTATE-SPECIFIC ANTIGEN (PSA)", Chemistry & biology, 5(9), 1998, pp. 475-488

Abstract

Background: The serine protease prostate-specific antigen (PSA) isa useful clinical marker for prostatic malignancy. PSA is a member of thekallikrein subgroup of the (chymo)trypsin serine protease family, butdiffers from the prototypical member of this subgroup, tissue kallikrein, in possessing a specificity more similar to that of chymotrypsin than trypsin. We report the use of two strategies, substrate phage display and iterative optimization of natural cleavage sites, to identifylabile sequences for PSA cleavage. Results: Iterative optimization and substrate phage display converged on the amino-acid sequence SS(Y/F)Y down arrow S(G/S) as preferred subsite occupancy for PSA. These sequences were cleaved by PSA with catalytic efficiencies as high as 2200-3100 M-1 s(-1), compared with values of 2-46 M-1 s(-1) for peptides containing likely physiological target sequences of PSA from the proteinsemenogelin. Substrate residues that bind to secondary (non-S1) subsites have a critical role in defining labile substrates and can even cause otherwise disfavored amino acids to bind in the primary specificity (S1) pocket. Conclusions: The importance of secondary subsites in defining both the specificity and efficiency of cleavage suggests that substrate recognition by PSA is mediated by an extended binding site. Elucidation of preferred subsite occupancy allowed refinement of the structural model of PSA and should facilitate the development of more sensitive activity-based assays and the design of potent inhibitors.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/11/20 alle ore 10:26:23