Structural insights into catalytic relevances of substrate poses in ACC-1

Da Woon Bae, Ye Eun Jung, Young Jun An, Jung Hyun Na, Sun Shin Cha

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


ACC-1 is a plasmid-encoded class C β-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 Ω loop, and the Phe119 loop located 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 C-4 carboxylate and N-5 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.

Original languageEnglish
Article numbere0141119
JournalAntimicrobial Agents and Chemotherapy
Issue number11
StatePublished - 2019

Bibliographical note

Publisher Copyright:
Copyright © 2019 American Society for Microbiology. All Rights Reserved.


  • ACC-1 class C β-lactamase
  • Acyl-enzyme complex
  • Adenylylation
  • Cefotaxime
  • Cefoxitin
  • Crystal structures


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