Secreted aspartic proteases of Candida albicans, Candida tropicalis, Candida parapsilosis and Candida lusitaniae. Inhibition with peptidomimetic inhibitors
Jazyk angličtina Země Velká Británie, Anglie Médium print
Typ dokumentu srovnávací studie, časopisecké články, práce podpořená grantem
PubMed
11322888
DOI
10.1046/j.1432-1327.2001.02152.x
PII: ejb2152
Knihovny.cz E-zdroje
- MeSH
- aspartátové endopeptidasy antagonisté a inhibitory genetika izolace a purifikace metabolismus MeSH
- Candida albicans enzymologie MeSH
- Candida enzymologie MeSH
- inhibitory proteas chemie farmakologie MeSH
- kinetika MeSH
- lidé MeSH
- molekulární sekvence - údaje MeSH
- pepstatiny chemie farmakologie MeSH
- sekvence aminokyselin MeSH
- sekvenční homologie aminokyselin MeSH
- substrátová specifita MeSH
- techniky in vitro MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- aspartátové endopeptidasy MeSH
- inhibitory proteas MeSH
- pepstatin MeSH Prohlížeč
- pepstatiny MeSH
- Streptomyces pepsin inhibitor MeSH Prohlížeč
The frequency of Candida infections has increased in recent years and it has been accompanied by a significant rise in morbidity and mortality. The secretion of aspartic proteases by Candida spp. was demonstrated to be one of the virulence determinants. Candida albicans is classified as the major human pathogen in the genus Candida. However, other species of this genus have been found to cause an increasing number of candidiases. We isolated secreted aspartic proteases (Saps) of C. albicans (Sap2p), C. tropicalis (Sapt1p), C. parapsilosis (Sapp1p), and C. lusitaniae (Saplp) from culture media. All the isolated proteases were N-terminally sequenced. Their specific proteolytic activities and sensitivity to series of peptidomimetic inhibitors modified in the type of scissile bond replacement as well as in the N- and C-termini were analyzed. The most divergent substrate specificity was observed for the Sap of C. tropicalis. The specificity of Sap of C. lusitaniae is most closely related to that of Sap of C. parapsilosis. We designed and prepared an inhibitor containing phenylstatine isoster that was equipotent towards all four proteases within the range of 10-10-10-9 M. The HIV-1 protease inhibitors ritonavir, saquinavir, indinavir, and nelfinavir were also tested for the inhibition of four Saps. Only ritonavir and saquinavir inhibited Sap2p, Sapt1p, Sapp1p, and Saplp in micromolar concentrations.
Citace poskytuje Crossref.org
SWISSPROT
P28871, P32951, Q00663
