Structure-Function Relationship of Aminopeptidase P from Pseudomonas aeruginosa
Structure-Function Relationship of Aminopeptidase P from Pseudomonas aeruginosa
复制标题
铜绿假单胞菌氨肽酶 P 的结构与功能关系
DOI：
10.3389/fmicb.2017.02385
复制
发表时间：
2017-12-05
影响因子：
5.2
通讯作者：
Bao, Rui
中科院分区：
文献类型：
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作者：
Peng, Cui-Ting;Liu, Li;Bao, Rui
PepP是铜绿假单胞菌中的毒力相关基因，使其成为抗铜绿假单胞菌药物开发的有吸引力的靶标。其编码蛋白为氨基肽酶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，功能性研究测量了不同金属离子对活性的影响。在活性中心观察到一个三金属锰簇，阐明了金属离子的抑制机制。此外，从活性位点延伸的环对于特异性大底物结合似乎是重要的。基于结构比较和细菌侵袭实验，我们发现这种非保守的表面环对于铜绿假单胞菌的毒力是至关重要的。综上所述，这些发现可以扩展我们对Pa-PepP的催化机制和毒力相关功能的理解，并为设计针对病原细菌感染的特异性抑制剂提供坚实的基础。
PepP is a virulence-associated gene in Pseudomonas aeruginosa, making it an attractive target for anti-P. aeruginosa 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 P. aeruginosa 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.