6KA5

Crystal structure of a class C beta-lactamase in complex with cefoxitin

Summary for 6KA5

• Entry DOI: 10.2210/pdb6ka5/pdb
• Descriptor: Beta-lactamase, (2R)-2-{(1S)-1-methoxy-2-oxo-1-[(thiophen-2-ylacetyl)amino]ethyl}-5-methylidene-5,6-dihydro-2H-1,3-thiazine-4-carboxylic acid (3 entities in total)
• Functional Keywords: class c-lactamase, acyl-enzyme complex, hydrolase
• Biological source: Klebsiella pneumoniae
• Total number of polymer chains: 1
• Total formula weight: 41081.74

Authors

Bae, D.W.,Jung, Y.E.,An, Y.J.,Na, J.H.,Cha, S.S. (deposition date: 2019-06-20, release date: 2019-10-16, Last modification date: 2023-11-29)

Primary citation

Bae, D.W.,Jung, Y.E.,An, Y.J.,Na, J.H.,Cha, S.S.
Structural Insights into Catalytic Relevances of Substrate Poses in ACC-1.
Antimicrob.Agents Chemother., 63:-, 2019

PubMed Abstract: ACC-1 is a plasmid-encoded class C β-lactamase identified in clinical isolates of , , , and 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.

PubMed: 31451494
DOI: 10.1128/AAC.01411-19

Experimental method

X-RAY DIFFRACTION (1.59 Å)