Biomol Ther.  2023 Mar;31(2):141-147. 10.4062/biomolther.2023.008.

Structural Insights for β-Lactam Antibiotics

• Kim D
• Kim S
• Kwon Y
• Kim Y
• Park H
• Kwak K
• Lee H
• Lee JH
• Jang KM
• Kim D
• Lee SH
• Kang LW

• KMID: 2539582
• DOI: http://doi.org/10.4062/biomolther.2023.008

Abstract

Antibiotic resistance has emerged as a global threat to modern healthcare systems and has nullified many commonly used antibiotics. β-Lactam antibiotics are among the most successful and occupy approximately two-thirds of the prescription antibiotic market. They inhibit the synthesis of the peptidoglycan layer in the bacterial cell wall by mimicking the D-Ala-D-Ala in the pentapeptide crosslinking neighboring glycan chains. To date, various β-lactam antibiotics have been developed to increase the spectrum of activity and evade drug resistance. This review emphasizes the three-dimensional structural characteristics of β-lactam antibiotics regarding the overall scaffold, working mechanism, chemical diversity, and hydrolysis mechanism by β-lactamases. The structural insight into various β-lactams will provide an in-depth understanding of the antibacterial efficacy and susceptibility to drug resistance in multidrug-resistant bacteria and help to develop better β-lactam antibiotics and inhibitors.

Keyword

Antibiotics; β-Lactams; Peptidoglycan; Antibiotic resistance; Serine β-lactamases; Metallo-β-lactamases