Premium
Structure and characterization of a NAD(P)H‐dependent carbonyl reductase from Pseudomonas aeruginosa PAO1
Author(s) -
Li Shanshan,
Teng Xiaozhen,
Su Li,
Mao Guannan,
Xu Yueyang,
Li Tingting,
Liu Riuhua,
Zhang Qionglin,
Wang Yingying,
Bartlam Mark
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12683
Subject(s) - nad+ kinase , protein data bank (rcsb pdb) , reductase , pseudomonas aeruginosa , protein data bank , chemistry , biochemistry , stereochemistry , accession number (library science) , structural similarity , active site , enzyme , pathogen , oxidoreductase , oxygenase , protein structure , bacteria , biology , microbiology and biotechnology , gene , genetics , genbank
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° 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. Database Structural data are available in the Protein Data Bank (PDB) under the following accession numbers: apo PA4079 (condition I), 5WQM ; apo PA4079 (condition II), 5WQN ; PA4079 + NADP (condition I), 5WQO ; PA4079 + NADP (condition II), 5WQP .