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The crystal structure of the secreted aspartic proteinase 3 from Candida albicans and its complex with pepstatin A
Author(s) -
Borelli Claudia,
Ruge Elisabeth,
Schaller Martin,
Monod Michel,
Korting Hans Christian,
Huber Robert,
Maskos Klaus
Publication year - 2007
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21425
Subject(s) - pepstatin , candida albicans , hydrolase , virulence factor , virulence , corpus albicans , microbiology and biotechnology , biology , enzyme , isozyme , chemistry , biochemistry , gene , protease
The family of secreted aspartic proteinases (Sap) encoded by 10 SAP genes is an important virulence factor during Candida albicans (C. albicans) infections. Antagonists to Saps could be envisioned to help prevent or treat candidosis in immunocompromised patients. The knowledge of several Sap structures is crucial for inhibitor design; only the structure of Sap2 is known. We report the 1.9 and 2.2 Å resolution X‐ray crystal structures of Sap3 in a stable complex with pepstatin A and in the absence of an inhibitor, shedding further light on the enzyme inhibitor binding. Inhibitor binding causes active site closure by the movement of a flap segment. Comparison of the structures of Sap3 and Sap2 identifies elements responsible for the specificity of each isoenzyme. Proteins 2007. © 2007 Wiley‐Liss, Inc.