6ka5
Crystal structure of a class C beta-lactamase in complex with cefoxitinCrystal structure of a class C beta-lactamase in complex with cefoxitin
Structural highlights
Publication Abstract from PubMedACC-1 is a plasmid-encoded class C beta-lactamase identified in clinical isolates of Klebsiella pneumoniae, Proteus mirabilis, Salmonella enterica, and Escherichia coli ACC-1-producing bacteria are susceptible to cefoxitin whereas they are resistant to oxyimino cephalosporins. Here, we depict crystal structures of apo ACC-1, adenylylated ACC-1, and acylated ACC-1 complexed with cefotaxime and cefoxitin. ACC-1 has noteworthy structural alterations in the R2-loop, the Omega- loop, and the Phe119-loop along the active-site rim. The adenylate covalently bonded to the nucleophilic serine reveals a tetrahedral phosphorus mimicking the deacylation transition state. Cefotaxime in ACC-1 has a proper conformation for the substrate-assisted catalysis in that its C4 carboxylate and N5 nitrogen are adequately located to facilitate the deacylation reaction. In contrast, cefoxitin in ACC-1 has a distinct conformation in which those functional groups cannot contribute to catalysis. Furthermore, the orientation of the deacylating water relative to the acyl carbonyl group in ACC-1 is unfavorable for nucleophilic attack. Structural insights into catalytic relevances of substrates' poses in ACC-1.,Bae DW, Jung YE, An YJ, Na JH, Cha SS Antimicrob Agents Chemother. 2019 Aug 26. pii: AAC.01411-19. doi:, 10.1128/AAC.01411-19. PMID:31451494[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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