The crystal structure of protease Sapp1p from Candida parapsilosis in complex with the HIV protease inhibitor ritonavir
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Aspartic Acid Endopeptidases antagonists & inhibitors chemistry MeSH
- Candida enzymology MeSH
- Fungal Proteins antagonists & inhibitors chemistry MeSH
- HIV Protease Inhibitors chemistry pharmacology MeSH
- Crystallography, X-Ray MeSH
- Models, Molecular MeSH
- Ritonavir chemistry pharmacology MeSH
- Structure-Activity Relationship MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Aspartic Acid Endopeptidases MeSH
- Fungal Proteins MeSH
- HIV Protease Inhibitors MeSH
- Ritonavir MeSH
- SAPP1 protein, Candida parapsilosis MeSH Browser
Secreted aspartic proteases (Saps) are extracellular proteolytic enzymes that enhance the virulence of Candida pathogens. These enzymes therefore represent possible targets for therapeutic drug design. Saps are inhibited by nanomolar concentrations of the classical inhibitor of aspartic proteases pepstatin A and also by the inhibitors of the HIV protease, but with the K(i) of micromolar values or higher. To contribute to the discussion regarding whether HIV protease inhibitors can act against opportunistic mycoses by the inhibition of Saps, we determined the structure of Sapp1p from Candida parapsilosis in complex with ritonavir (RTV), a clinically used inhibitor of the HIV protease. The crystal structure refined at resolution 2.4 Å proved binding of RTV into the active site of Sapp1p and provided the structural information necessary to evaluate the stability and specificity of the protein-inhibitor interaction.
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