Secreted aspartic proteases of Candida albicans, Candida tropicalis, Candida parapsilosis and Candida lusitaniae. Inhibition with peptidomimetic inhibitors
Language English Country England, Great Britain Media print
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
PubMed
11322888
DOI
10.1046/j.1432-1327.2001.02152.x
PII: ejb2152
Knihovny.cz E-resources
- MeSH
- Aspartic Acid Endopeptidases antagonists & inhibitors genetics isolation & purification metabolism MeSH
- Candida albicans enzymology MeSH
- Candida enzymology MeSH
- Protease Inhibitors chemistry pharmacology MeSH
- Kinetics MeSH
- Humans MeSH
- Molecular Sequence Data MeSH
- Pepstatins chemistry pharmacology MeSH
- Amino Acid Sequence MeSH
- Sequence Homology, Amino Acid MeSH
- Substrate Specificity MeSH
- In Vitro Techniques MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- Aspartic Acid Endopeptidases MeSH
- Protease Inhibitors MeSH
- pepstatin MeSH Browser
- Pepstatins MeSH
- Streptomyces pepsin inhibitor MeSH Browser
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.
References provided by Crossref.org
SWISSPROT
P28871, P32951, Q00663
