1. Atomic resolution crystal structure of Sapp2p, a secreted aspartic protease from Candida parapsilosis.
- Author
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Dostál J, Pecina A, Hrušková-Heidingsfeldová O, Marečková L, Pichová I, Řezáčová P, Lepšík M, and Brynda J
- Subjects
- Amino Acid Sequence, Aspartic Acid Proteases genetics, Aspartic Acid Proteases isolation & purification, Aspartic Acid Proteases metabolism, Candida enzymology, Candida genetics, Catalytic Domain, Crystallography, X-Ray, Fungal Proteins genetics, Fungal Proteins isolation & purification, Fungal Proteins metabolism, Gene Expression, Isoenzymes chemistry, Isoenzymes genetics, Isoenzymes isolation & purification, Isoenzymes metabolism, Kinetics, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Structure, Secondary, Quantum Theory, Sequence Alignment, Structural Homology, Protein, Substrate Specificity, Thermodynamics, Aspartic Acid Proteases chemistry, Candida chemistry, Fungal Proteins chemistry, Pepstatins chemistry, Protease Inhibitors chemistry
- Abstract
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.
- Published
- 2015
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