7tz4

Publication Abstract from PubMed

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 A when co-crystallized with the adenylation inhibitor 5'-O-(N-salicylsulfamoyl)adenosine (salicyl-AMS) and to 1.69 A 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.

Rational inhibitor design for Pseudomonas aeruginosa salicylate adenylation enzyme PchD.,Shelton CL, Meneely KM, Ronnebaum TA, Chilton AS, Riley AP, Prisinzano TE, Lamb AL J Biol Inorg Chem. 2022 May 5. pii: 10.1007/s00775-022-01941-8. doi:, 10.1007/s00775-022-01941-8. PMID:35513576^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.