Rational inhibitor design for Pseudomonas aeruginosa salicylate adenylation enzyme PchD
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Issue Date
2022-05-05Author
Shelton, Catherine L.
Meneely, Kathleen M.
Ronnebaum, Trey A.
Chilton, Annemarie S.
Riley, Andrew P.
Prisinzano, Thomas E.
Lamb, Audrey L.
Publisher
Springer
Type
Article
Article Version
Scholarly/refereed, publisher version
Rights
© The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License.
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Show full item recordAbstract
Pseudomonas aeruginosa is an increasingly antibiotic-resistant pathogen that causes severe lung infections, burn wound infections, and diabetic foot infections. P. aeruginosa produces the siderophore pyochelin through the use of a non-ribosomal peptide synthetase (NRPS) biosynthetic pathway. Targeting members of siderophore NRPS proteins is one avenue currently under investigation for the development of new antibiotics against antibiotic-resistant organisms. Here, the crystal structure of the pyochelin adenylation domain PchD is reported. The structure was solved to 2.11 Å when co-crystallized with the adenylation inhibitor 5′-O-(N-salicylsulfamoyl)adenosine (salicyl-AMS) and to 1.69 Å with a modified version of salicyl-AMS designed to target an active site cysteine (4-cyano-salicyl-AMS). In the structures, PchD adopts the adenylation conformation, similar to that reported for AB3403 from Acinetobacter baumannii.
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Citation
Shelton, C.L., Meneely, K.M., Ronnebaum, T.A. et al. Rational inhibitor design for Pseudomonas aeruginosa salicylate adenylation enzyme PchD. J Biol Inorg Chem 27, 541–551 (2022). https://doi.org/10.1007/s00775-022-01941-8
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