Structure and characterization of a NAD(P)H-dependent carbonyl reductase from Pseudomonas aeruginosa PAO1

被引:7
作者
Li, Shanshan [1 ,2 ]
Teng, Xiaozhen [1 ,2 ]
Su, Li [3 ]
Mao, Guannan [3 ]
Xu, Yueyang [2 ]
Li, Tingting [1 ,2 ]
Liu, Riuhua [2 ]
Zhang, Qionglin [2 ]
Wang, Yingying [3 ]
Bartlam, Mark [1 ,2 ]
机构
[1] Nankai Univ, State Key Lab Med Chem Biol, Tianjin, Peoples R China
[2] Nankai Univ, Coll Life Sci, Tianjin, Peoples R China
[3] Nankai Univ, Minist Educ, Key Lab Pollut Proc & Environm Criteria, Coll Environm Sci & Engn, Tianjin, Peoples R China
基金
中国国家自然科学基金;
关键词
carbonyl reductase; crystal structure; opportunistic pathogen; PA4079; Pseudomonas aeruginosa; short-chain dehydrogenase/reductase; ANTIMICROBIAL RESISTANCE; BIOFILMS; FEATURES; PURIFICATION; EXPRESSION; SEQUENCE; GENE;
D O I
10.1002/1873-3468.12683
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
To investigate the function of the pa4079 gene from the opportunistic pathogen Pseudomonas aeruginosa PAO1, we determined its crystal structure and confirmed it to be a NAD(P)-dependent short-chain dehydrogenase/reductase. Structural similarity and activity for a broad range of substrates indicate that PA4079 functions as a carbonyl reductase. Comparison of apo- and holo-PA4079 shows that NADP stabilizes the active site specificity loop, and small molecule binding induces rotation of the Tyr183 side chain by approximately 90 degrees out of the active site. Quantitative real-time PCR results show that pa4079 maintains high expression levels during antibiotic exposure. This work provides a starting point for understanding substrate recognition and selectivity by PA4079, as well as its possible reduction of antimicrobial drugs.
引用
收藏
页码:1785 / 1797
页数:13
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