biostudies-literatureKim DMinistry of Science and ICTMinistry of Oceans and FisheriesNational Research Foundation of Korea141-147https://www.ebi.ac.uk/biostudies/studies/S-EPMC9970833biostudies-literatureUnknown31(2)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.Biomolecules & therapeuticsStructural Insights for β-Lactam Antibiotics.PMC9970833NRF-2017M3A9E4078014 and NRF-2017M3A9E407801720170305Kim SKim DPark HJang KMKwak KLee SHKwon YKim YLee HKang LWLee JHfalseStructural Insights for β-Lactam Antibiotics.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.2023-01-01T00:00:00Z2023 Mar2025-04-19T02:43:43.986Z2025-02-19T04:54:58.315ZS-EPMC99708333678865410.4062/biomolther.2023.008