Atomic resolution crystal structure of Sapp2p, a secreted aspartic protease from Candida parapsilosis
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
26627656
DOI
10.1107/s1399004715019392
PII: S1399004715019392
Knihovny.cz E-resources
- Keywords
- Candida parapsilosis, Sapp2p, aspartic protease, crystal structure, interaction energy, quantum mechanics, ultrahigh resolution,
- MeSH
- Aspartic Acid Proteases chemistry genetics isolation & purification metabolism MeSH
- Candida chemistry enzymology genetics MeSH
- Gene Expression MeSH
- Fungal Proteins chemistry genetics isolation & purification metabolism MeSH
- Protease Inhibitors chemistry MeSH
- Isoenzymes chemistry genetics isolation & purification metabolism MeSH
- Catalytic Domain MeSH
- Kinetics MeSH
- Crystallography, X-Ray MeSH
- Quantum Theory MeSH
- Models, Molecular MeSH
- Molecular Sequence Data MeSH
- Pepstatins chemistry MeSH
- Protein Structure, Secondary MeSH
- Amino Acid Sequence MeSH
- Sequence Alignment MeSH
- Structural Homology, Protein MeSH
- Substrate Specificity MeSH
- Thermodynamics MeSH
- Protein Binding MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Aspartic Acid Proteases MeSH
- Fungal Proteins MeSH
- Protease Inhibitors MeSH
- Isoenzymes MeSH
- pepstatin MeSH Browser
- Pepstatins MeSH
The virulence of the Candida pathogens is enhanced by the production of secreted aspartic proteases, which therefore represent possible targets for drug design. Here, the crystal structure of the secreted aspartic protease Sapp2p from Candida parapsilosis was determined. Sapp2p was isolated from its natural source and crystallized in complex with pepstatin A, a classical aspartic protease inhibitor. The atomic resolution of 0.83 Å allowed the protonation states of the active-site residues to be inferred. A detailed comparison of the structure of Sapp2p with the structure of Sapp1p, the most abundant C. parapsilosis secreted aspartic protease, was performed. The analysis, which included advanced quantum-chemical interaction-energy calculations, uncovered molecular details that allowed the experimentally observed equipotent inhibition of both isoenzymes by pepstatin A to be rationalized.
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