AUTHOR=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 

TITLE=Structure–Function Relationship of Aminopeptidase P from Pseudomonas aeruginosa

JOURNAL=Frontiers in Microbiology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2017.02385

DOI=10.3389/fmicb.2017.02385

ISSN=1664-302X

ABSTRACT=<p><italic>PepP</italic> is a virulence-associated gene in <italic>Pseudomonas aeruginosa</italic>, making it an attractive target for anti<italic>-P. aeruginosa</italic> 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 <italic>P. aeruginosa</italic> 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.</p>