Liu Xiang-Qin, Yang Jing
Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, NS, Canada B3H 4H7.
FEBS Lett. 2004 Aug 13;572(1-3):46-50. doi: 10.1016/j.febslet.2004.07.016.
Inteins are self-splicing intervening sequences in proteins, and inteins of pathogenic organisms can be attractive drug targets. Here, we report an intein in important fungal pathogens including Aspergillus fumigatus, Aspergillus nidulans, Histoplasma capsulatum, and different serotypes of Cryptococcus neoformans. This intein is inside the extremely conserved and functionally essential Prp8 protein, and it varies in size from 170 aa in C. neoformans to 819 aa in A. fumigatus, which is caused by the presence or absence of an endonuclease domain and a putative tongs subdomain in the intein. Prp8 inteins of these organisms were demonstrated to do protein splicing in a recombinant protein in Escherichia coli. These findings revealed Prp8 inteins as attractive targets for potential antifungal drugs to be identified using existing selection and screening methods.
内含肽是蛋白质中的自我剪接间隔序列,致病生物的内含肽可能是有吸引力的药物靶点。在此,我们报道了重要真菌病原体中的一种内含肽,这些病原体包括烟曲霉、构巢曲霉、荚膜组织胞浆菌以及新型隐球菌的不同血清型。这种内含肽存在于极度保守且功能关键的Prp8蛋白内部,其大小在新型隐球菌中为170个氨基酸,在烟曲霉中为819个氨基酸,这种差异是由内含肽中是否存在核酸内切酶结构域和一个假定的钳状亚结构域导致的。这些生物的Prp8内含肽在大肠杆菌的重组蛋白中被证明能进行蛋白质剪接。这些发现揭示了Prp8内含肽是利用现有筛选方法鉴定潜在抗真菌药物的有吸引力的靶点。