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7U57

apo-CTX-M-15

Summary for 7U57
Entry DOI10.2210/pdb7u57/pdb
DescriptorBeta-lactamase, SULFATE ION (3 entities in total)
Functional Keywordsantibiotics, apo, b-lactamase, ctx-m-15, structural protein
Biological sourceEscherichia coli
Total number of polymer chains3
Total formula weight93854.01
Authors
Ahmadvand, P.,Kang, C.H. (deposition date: 2022-03-01, release date: 2022-05-25, Last modification date: 2023-10-18)
Primary citationAhmadvand, P.,Avillan, J.J.,Lewis, J.A.,Call, D.R.,Kang, C.
Characterization of Interactions between CTX-M-15 and Clavulanic Acid, Desfuroylceftiofur, Ceftiofur, Ampicillin, and Nitrocefin.
Int J Mol Sci, 23:-, 2022
Cited by
PubMed Abstract: Cefotaximase-Munich (CTX-M) extended-spectrum beta-lactamases (ESBLs) are commonly associated with Gram-negative, hospital-acquired infections worldwide. Several beta-lactamase inhibitors, such as clavulanate, are used to inhibit the activity of these enzymes. To understand the mechanism of CTX-M-15 activity, we have determined the crystal structures of CTX-M-15 in complex with two specific classes of beta-lactam compounds, desfuroylceftiofur (DFC) and ampicillin, and an inhibitor, clavulanic acid. The crystal structures revealed that Ser70 and five other residues (Lys73, Tyr105, Glu166, Ser130, and Ser237) participate in catalysis and binding of those compounds. Based on analysis of steady-state kinetics, thermodynamic data, and molecular docking to both wild-type and S70A mutant structures, we determined that CTX-M-15 has a similar affinity for all beta-lactam compounds (ceftiofur, nitrocefin, DFC, and ampicillin), but with lower affinity for clavulanic acid. A catalytic mechanism for tested β-lactams and two-step inhibition mechanism of clavulanic acid were proposed. CTX-M-15 showed a higher activity toward DFC and nitrocefin, but significantly lower activity toward ampicillin and ceftiofur. The interaction between CTX-M-15 and both ampicillin and ceftiofur displayed a higher entropic but lower enthalpic effect, compared with DFC and nitrocefin. DFC, a metabolite of ceftiofur, displayed lower entropy and higher enthalpy than ceftiofur. This finding suggests that compounds containing amine moiety (e.g., ampicillin) and the furfural moiety (e.g., ceftiofur) could hinder the hydrolytic activity of CTX-M-15.
PubMed: 35563620
DOI: 10.3390/ijms23095229
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.37 Å)
Structure validation

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