title: Atomic resolution crystal structure of Sapp2p, a secreted aspartic protease from Candida parapsilosis.
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.
authors.affiliation: Institute of Organic Chemistry and Biochemistry (IOCB), Academy of Sciences of the Czech Republic, Flemingovo náměstí 2, 166 10 Prague 6, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Dostál
authors.affiliation: Institute of Organic Chemistry and Biochemistry (IOCB), Academy of Sciences of the Czech Republic, Flemingovo náměstí 2, 166 10 Prague 6, Czech Republic.
authors.forename: Adam
authors.initials: A
authors.lastname: Pecina
authors.affiliation: Institute of Organic Chemistry and Biochemistry (IOCB), Academy of Sciences of the Czech Republic, Flemingovo náměstí 2, 166 10 Prague 6, Czech Republic.
authors.forename: Olga
authors.initials: O
authors.lastname: Hrušková-Heidingsfeldová
authors.affiliation: Institute of Organic Chemistry and Biochemistry (IOCB), Academy of Sciences of the Czech Republic, Flemingovo náměstí 2, 166 10 Prague 6, Czech Republic.
authors.forename: Lucie
authors.initials: L
authors.lastname: Marečková
authors.affiliation: Institute of Organic Chemistry and Biochemistry (IOCB), Academy of Sciences of the Czech Republic, Flemingovo náměstí 2, 166 10 Prague 6, Czech Republic.
authors.forename: Iva
authors.initials: I
authors.lastname: Pichová
authors.affiliation: Institute of Organic Chemistry and Biochemistry (IOCB), Academy of Sciences of the Czech Republic, Flemingovo náměstí 2, 166 10 Prague 6, Czech Republic.
authors.forename: Pavlina
authors.initials: P
authors.lastname: Řezáčová
authors.affiliation: Institute of Organic Chemistry and Biochemistry (IOCB), Academy of Sciences of the Czech Republic, Flemingovo náměstí 2, 166 10 Prague 6, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Lepšík
authors.affiliation: Institute of Organic Chemistry and Biochemistry (IOCB), Academy of Sciences of the Czech Republic, Flemingovo náměstí 2, 166 10 Prague 6, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Brynda
mesh_terms: D000595:Amino Acid Sequence; D057055:Aspartic Acid Proteases / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D002175:Candida / Q000737:chemistry* / Q000201:enzymology / Q000235:genetics; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D015870:Gene Expression; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010436:Pepstatins / Q000737:chemistry*; D011480:Protease Inhibitors / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011789:Quantum Theory; D016415:Sequence Alignment; D040681:Structural Homology, Protein; D013379:Substrate Specificity; D013816:Thermodynamics
chemical_list: D005656:Fungal Proteins; D007527:Isoenzymes; D010436:Pepstatins; D011480:Protease Inhibitors; D057055:Aspartic Acid Proteases; C031375:pepstatin
keywords: Candida parapsilosis; Sapp2p; aspartic protease; crystal structure; interaction energy; quantum mechanics; ultrahigh resolution