{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Beer M"],"funding":["BLRD VA","Cleveland Department of Veterans Affairs","European Research Council","Biotechnology and Biological Sciences Research Council","Engineering and Physical Sciences Research Council"],"pagination":["3284-3300"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12643063"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["599(22)"],"pubmed_abstract":["β-Lactamase-catalysed hydrolysis is the primary form of β-lactam antibiotic resistance in Gram-negative bacteria. The penicillanic acid sulfone (PAS) enmetazobactam is thought to inhibit extended-spectrum β-lactamases (ESBLs) by fragmentation of an initial acyl-enzyme to form an active-site lysinoalanine cross link. We investigate interactions of enmetazobactam and its congener tazobactam with GES-1, an ESBL with structural features of carbapenem-hydrolysing β-lactamases. Crystal structures show different breakdown products of the two inhibitors covalently bound to the catalytic Ser70, assigned using quantum mechanics/molecular mechanics (QM/MM) calculations. We find no evidence for lysinoalanine formation, with mass spectrometry indicating active enzyme regeneration, behaviour previously "],"journal":["FEBS letters"],"pubmed_title":["Mechanistic basis for inhibition of the extended-spectrum β-lactamase GES-1 by enmetazobactam and tazobactam."],"pmcid":["PMC12643063"],"funding_grant_id":["BB/M026280/1","BB/T008741/1","1I01BX001974","EP/W013738/1","I01 BX001974","101021207"],"pubmed_authors":["Papp-Wallace KM","Beer M","Mulholland AJ","Spencer J","Bethel CR","Shapiro S","Hinchliffe P","Hanzevacki M","Tooke CL","Van der Kamp MW","Bonomo RA"],"additional_accession":[]},"is_claimable":false,"name":"Mechanistic basis for inhibition of the extended-spectrum β-lactamase GES-1 by enmetazobactam and tazobactam.","description":"β-Lactamase-catalysed hydrolysis is the primary form of β-lactam antibiotic resistance in Gram-negative bacteria. The penicillanic acid sulfone (PAS) enmetazobactam is thought to inhibit extended-spectrum β-lactamases (ESBLs) by fragmentation of an initial acyl-enzyme to form an active-site lysinoalanine cross link. We investigate interactions of enmetazobactam and its congener tazobactam with GES-1, an ESBL with structural features of carbapenem-hydrolysing β-lactamases. Crystal structures show different breakdown products of the two inhibitors covalently bound to the catalytic Ser70, assigned using quantum mechanics/molecular mechanics (QM/MM) calculations. We find no evidence for lysinoalanine formation, with mass spectrometry indicating active enzyme regeneration, behaviour previously ","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-06-05T16:51:50.471Z","creation":"2026-05-19T03:11:56.287Z"},"accession":"S-EPMC12643063","cross_references":{"pubmed":["40944392"],"doi":["10.1002/1873-3468.70155"]}}