Peng Cui-Ting, Liu Li, Li Chang-Cheng, He Li-Hui, Li Tao, Shen Ya-Lin, Gao Chao, Wang Ning-Yu, Xia Yong, Zhu Yi-Bo, Song Ying-Jie, Lei Qian, Yu Luo-Ting, Bao Rui
Pharmaceutical and Biological Engineering Department, School of Chemical Engineering, Sichuan University, Chengdu, China.
Center of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, China.
Front Microbiol. 2017 Dec 5;8:2385. doi: 10.3389/fmicb.2017.02385. eCollection 2017.
is a virulence-associated gene in , making it an attractive target for anti drug development. The encoded protein, aminopeptidases P (Pa-PepP), is a type of X-prolyl peptidase that possesses diverse biological functions. The crystal structure verified its canonical pita-bread fold and functional tetrameric assembly, and the functional studies measured the influences of different metal ions on the activity. A trimetal manganese cluster was observed at the active site, elucidating the mechanism of inhibition by metal ions. Additionally, a loop extending from the active site appeared to be important for specific large-substrate binding. Based on the structural comparison and bacterial invasion assays, we showed that this non-conserved surface loop was critical for virulence. Taken together, these findings can extend our understanding of the catalytic mechanism and virulence-related functions of Pa-PepP and provide a solid foundation for the design of specific inhibitors against pathogenic-bacterial infections.
是一种与毒力相关的基因，使其成为抗药物开发的一个有吸引力的靶点。编码的蛋白质，氨肽酶P（Pa-PepP），是一种具有多种生物学功能的X-脯氨酰肽酶。晶体结构验证了其典型的皮塔饼折叠和功能性四聚体组装，功能研究测量了不同金属离子对活性的影响。在活性位点观察到一个三金属锰簇，阐明了金属离子的抑制机制。此外，从活性位点延伸出的一个环似乎对特定大底物的结合很重要。基于结构比较和细菌侵袭试验，我们表明这个非保守的表面环对毒力至关重要。综上所述，这些发现可以扩展我们对Pa-PepP催化机制和毒力相关功能的理解，并为设计针对病原菌感染的特异性抑制剂提供坚实的基础。
