5UJO

X-Ray Crystal Structure of Ruthenocenyl-7-Aminodesacetoxycephalosporanic Acid Covalent Acyl-Enyzme Complex with CTX-M-14 E166A Beta-Lactamase

Summary for 5UJO

• Entry DOI: 10.2210/pdb5ujo/pdb
• Descriptor: Beta-lactamase, POTASSIUM ION, ruthenocenyl-7-aminodesacetoxycephalosporanic acid, bound form, ... (5 entities in total)
• Functional Keywords: beta-lactamase, organometallic, ruthenocene, ctx-m-14, hydrolase
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 58091.33

Authors

Lewandowski, E.M.,Chen, Y. (deposition date: 2017-01-18, release date: 2017-02-08, Last modification date: 2024-10-23)

Primary citation

Lewandowski, E.M.,Szczupak, L.,Wong, S.,Skiba, J.,Guspiel, A.,Solecka, J.,Vrcek, V.,Kowalski, K.,Chen, Y.
Antibacterial Properties of Metallocenyl-7-ADCA Derivatives and Structure in Complex with CTX-Mbeta-Lactamase.
Organometallics, 36:1673-1676, 2017

PubMed Abstract: A series of six novel metallocenyl-7-ADCA (metallocenyl = ferrocenyl or ruthenocenyl; 7-ADCA = 7-aminodesacetoxycephalosporanic acid) conjugates were synthesized and their antibacterial properties evaluated by biochemical and microbiological assays. The ruthenocene derivatives showed a higher level of inhibition of DD-carboxypeptidase 64-575, a Penicillin Binding Protein (PBP), than the ferrocene derivatives and the reference compound penicillin G. Protein X-ray crystallographic analysis revealed a covalent acyl-enzyme complex of a ruthenocenyl compound with CTX-M β-lactamase E166A mutant, corresponding to a similar complex with PBPs responsible for the bactericidal activities of these compounds. Most interestingly, an intact compound was captured at the crystal-packing interface, elucidating for the first time the structure of a metallocenyl β-lactam compound that previously eluded small molecule crystallography. We propose that protein crystals, even from biologically unrelated molecules, can be utilized to determine structures of small molecules.

PubMed: 29051683
DOI: 10.1021/acs.organomet.6b00888

Experimental method

X-RAY DIFFRACTION (1.35 Å)