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Structural Insights into Catalytic Relevances of Substrate Poses in ACC-1
- Title
- Structural Insights into Catalytic Relevances of Substrate Poses in ACC-1
- Authors
- Bae, Da-Woon; Jung, Ye-Eun; An, Young Jun; Na, Jung-Hyun; Cha, Sun-Shin
- Ewha Authors
- 차선신
- SCOPUS Author ID
- 차선신
- Issue Date
- 2019
- Journal Title
- ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
- ISSN
- 0066-4804
1098-6596
- Citation
- ANTIMICROBIAL AGENTS AND CHEMOTHERAPY vol. 63, no. 11
- Keywords
- crystal structures; ACC-1 class C beta-lactamase; adenylylation; acyl-enzyme complex; cefotaxime; cefoxitin
- Publisher
- AMER SOC MICROBIOLOGY
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- ACC-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 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.
- DOI
- 10.1128/AAC.01411-19
- Appears in Collections:
- 자연과학대학 > 화학·나노과학전공 > Journal papers
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