6RPN

Structure of metallo beta lactamase VIM-2 with cyclic boronate APC308.

Summary for 6RPN

• Entry DOI: 10.2210/pdb6rpn/pdb
• Related: 5FQC
• Descriptor: Beta-lactamase VIM-2, (3~{R})-2,2-bis(oxidanyl)-3-(phenylmethylsulfanyl)-3,4-dihydro-1,2-benzoxaborinin-2-ium-8-carboxylic acid, (3~{S})-2,2-bis(oxidanyl)-3-(phenylmethylsulfanyl)-3,4-dihydro-1,2-benzoxaborinin-2-ium-8-carboxylic acid, ... (8 entities in total)
• Functional Keywords: beta lactamases, antimicrobial resistance, cyclic boronate, antimicrobial protein
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 2
• Total formula weight: 53386.63

Authors

Parkova, A.,Lucic, A.,Brem, J.,McDonough, M.A.,Langley, G.W.,Schofield, C.J. (deposition date: 2019-05-14, release date: 2020-03-25, Last modification date: 2024-01-24)

Primary citation

Parkova, A.,Lucic, A.,Krajnc, A.,Brem, J.,Calvopina, K.,Langley, G.W.,McDonough, M.A.,Trapencieris, P.,Schofield, C.J.
Broad Spectrum beta-Lactamase Inhibition by a Thioether Substituted Bicyclic Boronate.
Acs Infect Dis., 6:1398-1404, 2020

PubMed Abstract: β-Lactamases comprise the most widely used mode of resistance to β-lactam antibiotics. Cyclic boronates have shown promise as a new class of β-lactamase inhibitor, with pioneering potential to potently inhibit both metallo- and serine-β-lactamases. We report studies concerning a bicyclic boronate ester with a thioether rather than the more typical β-lactam antibiotic "C-6/C-7" acylamino type side chain, which is present in the penicillin/cephalosporin antibiotics. The thioether bicyclic boronate ester was tested for activity against representative serine- and metallo-β-lactamases. The results support the broad inhibition potential of bicyclic boronate based inhibitors with different side chains, including against metallo-β-lactamases from B1, B2, and B3 subclasses. Combined with previous crystallographic studies, analysis of a crystal structure of the thioether inhibitor with the clinically relevant VIM-2 metallo-β-lactamase implies that further SAR work will expand the already broad scope of β-lactamase inhibition by bicyclic boronates.

PubMed: 31841636
DOI: 10.1021/acsinfecdis.9b00330

Experimental method

X-RAY DIFFRACTION (1.409 Å)