Atomic resolution crystal structure of Sapp2p, a secreted aspartic protease from Candida parapsilosis

0454168 - ÚOCHB 2016 RIV DK eng J - Článek v odborném periodiku
Dostál, Jiří - Pecina, Adam - Hrušková-Heidingsfeldová, Olga - Marečková, L. - Pichová, Iva - Řezáčová, Pavlína - Lepšík, Martin - Brynda, Jiří
Atomic resolution crystal structure of Sapp2p, a secreted aspartic protease from Candida parapsilosis.
Acta Crystallographica Section D-Biological Crystallography. Roč. 71, č. 12 (2015), s. 2494-2504. ISSN 1399-0047. E-ISSN 2059-7983
Grant CEP: GA ČR(CZ) GA14-23022S
Institucionální podpora: RVO:61388963 ; RVO:68378050
Klíčová slova: aspartic protease * Candida parapsilosis * Sapp2p * crystal structure * ultrahigh resolution * interaction energy * quantum mechanics
Kód oboru RIV: CE - Biochemie; EB - Genetika a molekulární biologie (UMG-J)
Impakt faktor: 2.512, rok: 2015

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 angstrom 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.
Trvalý link: http://hdl.handle.net/11104/0254881