Borelli Claudia, Ruge Elisabeth, Schaller Martin, Monod Michel, Korting Hans Christian, Huber Robert, Maskos Klaus
Department of Dermatology and Allergy, Ludwig Maximilian University of Munich, Frauenlobstr. 9-11, 80337 Munich, Germany.
Proteins. 2007 Aug 15;68(3):738-48. doi: 10.1002/prot.21425.
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.
由10个SAP基因编码的分泌型天冬氨酸蛋白酶（Sap）家族是白色念珠菌感染过程中的一个重要毒力因子。可以设想，Sap拮抗剂有助于预防或治疗免疫功能低下患者的念珠菌病。了解几种Sap的结构对于抑制剂设计至关重要；目前仅知道Sap2的结构。我们报告了Sap3与胃蛋白酶抑制剂A形成稳定复合物以及在无抑制剂情况下的1.9埃和2.2埃分辨率的X射线晶体结构，这进一步揭示了酶与抑制剂的结合情况。抑制剂结合通过一个瓣状片段的移动导致活性位点关闭。比较Sap3和Sap2的结构可确定每种同工酶特异性的相关元件。
