The crystal structure of the secreted aspartic proteinase 3 from Candida albicans and its complex with pepstatin A.
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 A 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.
Borelli
Claudia
C
Department of Dermatology and Allergy, Ludwig Maximilian University of Munich, Frauenlobstr. 9-11, 80337 Munich, Germany. claudia.borelli@med.uni-muenchen.de
Ruge
Elisabeth
E
Schaller
Martin
M
Monod
Michel
M
Korting
Hans Christian
HC
Huber
Robert
R
Maskos
Klaus
K
D016282:Aspartic Acid Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D002176:Candida albicans / Q000201:enzymology*; D018360:Crystallography, X-Ray; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D008958:Models, Molecular; D010436:Pepstatins / Q000737:chemistry*; D010843:Pichia / Q000235:genetics; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D013379:Substrate Specificity
D005656:Fungal Proteins; D010436:Pepstatins; D011994:Recombinant Proteins; D016282:Aspartic Acid Endopeptidases; C090754:SAP3 protein, Candida albicans; C031375:pepstatin