7tyb
Salicylate Adenylate PchD from Pseudomonas aeruginosa containing salicyl-AMSSalicylate Adenylate PchD from Pseudomonas aeruginosa containing salicyl-AMS
Structural highlights
FunctionPCHD_PSEAE Involved in the biosynthesis of the siderophore pyochelin (PubMed:8982005). Specifically adenylates salicylate and loads it onto the holo form of PchE via a thioester linkage to the phosphopanthetheine moiety (By similarity). Is also involved in the synthesis of the antifungal antibiotic dihydroaeruginoic acid (Dha or hydroxyphenyl-thiazolinyl-carboxylate), a precursor of pyochelin (PubMed:8982005).[UniProtKB:A0A0H2ZF83][1] Publication Abstract from PubMedPseudomonas 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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