{"doi":"10.1098/rstb.1980.0046","title":"The active centres in penicillin-sensitive enzymes","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>The interaction between β-lactam antibiotics and the penicillin-sensitive enzymes is a multiple-step process. Binding of the β-lactam ring of the penam (or 3-cephem) nucleus occurs at binding site no. 1. Interaction between the N-14 substituent of the bound molecule and binding site no. 2 induces changes in binding site no. 1. In turn, the catalytic site thus created increases the chemical reactivity of the β-lactam amide bond. As the β-lactam ring opens and acylates an enzyme serine residue, the interaction between the thiazolidine (or dihydrothiazine) ring and binding site no. 3 stabilizes the acyl-enzyme complex. Enzyme regeneration slowly proceeds either by direct elimi­ nation of the penicilloyl moiety or via G-5-C-6 splitting of the bound metabolite. The fragment arising from thiazolidine yields free iV-formyl-D-penicillamine while the enzyme-linked N-acylglycyl fragment is immediately attacked by an exogenous nucleophile correctly positioned on the acceptor site. Similarly, the enzyme action on L-X-D-Ala-D-Ala terminated peptides is mediated via a binding site no. 1 that com­- bines with D-Ala-D-Ala, a binding site no. 2 that interacts with the side chain of the preceding L-residue, an inducible catalytic site and an acceptor site. Enzymes are known that form a transitory L-X-D-Ala-enzyme complex where the acyl group is ester-linked to the same serine residue as that involved in the formation of the peni- cilloyl-enzyme complex (Waxman et al., this symposium). Other enzymes, however, may function as catalyst templates. Depending on the enzymes, the independence of the β-lactam and L-X-D-Ala-D-Ala active centres is more or less pronounced.</jats:p>","journal":"Philosophical Transactions of the Royal Society of London. B, Biological Sciences","year":1980,"id":662669,"datarank":0.4493598410330987,"base_score":2.995732273553991,"endowment":2.995732273553991,"self_citation_contribution":0.4493598410330987,"citation_network_contribution":0.0,"self_endowment_contribution":0.4493598410330987,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1730026,"name":"J.- M. Frère","orcid":null,"position":1,"is_corresponding":false},{"id":1730027,"name":"M. Leyh-Bouille","orcid":null,"position":2,"is_corresponding":false},{"id":1730028,"name":"H. R. Perkins","orcid":null,"position":3,"is_corresponding":false},{"id":1730029,"name":"M. Nieto","orcid":null,"position":4,"is_corresponding":false},{"id":1730025,"name":"J. - M. Ghuysen","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The active centres in penicillin-sensitive enzymes","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>The interaction between β-lactam antibiotics and the penicillin-sensitive enzymes is a multiple-step process. Binding of the β-lactam ring of the penam (or 3-cephem) nucleus occurs at binding site no. 1. Interaction between the N-14 substituent of the bound molecule and binding site no. 2 induces changes in binding site no. 1. In turn, the catalytic site thus created increases the chemical reactivity of the β-lactam amide bond. As the β-lactam ring opens and acylates an enzyme serine residue, the interaction between the thiazolidine (or dihydrothiazine) ring and binding site no. 3 stabilizes the acyl-enzyme complex. Enzyme regeneration slowly proceeds either by direct elimi­ nation of the penicilloyl moiety or via G-5-C-6 splitting of the bound metabolite. The fragment arising from thiazolidine yields free iV-formyl-D-penicillamine while the enzyme-linked N-acylglycyl fragment is immediately attacked by an exogenous nucleophile correctly positioned on the acceptor site. Similarly, the enzyme action on L-X-D-Ala-D-Ala terminated peptides is mediated via a binding site no. 1 that com­- bines with D-Ala-D-Ala, a binding site no. 2 that interacts with the side chain of the preceding L-residue, an inducible catalytic site and an acceptor site. Enzymes are known that form a transitory L-X-D-Ala-enzyme complex where the acyl group is ester-linked to the same serine residue as that involved in the formation of the peni- cilloyl-enzyme complex (Waxman et al., this symposium). Other enzymes, however, may function as catalyst templates. Depending on the enzymes, the independence of the β-lactam and L-X-D-Ala-D-Ala active centres is more or less pronounced.</jats:p>","is_dataset_classified":null,"base_score":2.995732273553991,"endowment":2.995732273553991,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"6109324","pmcid":null,"openalex_id":"https://openalex.org/W2146153230","authors":[],"funders":[{"funder_name":"NIAID NIH HHS","grant_id":"1 RO1 AI 13364-03","title":null}],"total_grants":1,"fwci":1.1808,"citation_percentile":0.77863299,"influential_citations":0,"citation_trend":[{"year":2020,"count":1}],"oa_status":"green","license":"other-oa","oa_locations":[{"url":"https://orbi.uliege.be/handle/2268/91671","host_type":"repository"},{"url":"https://orbi.uliege.be/handle/2268/91671","host_type":"repository"},{"url":"https://royalsocietypublishing.org/doi/pdf/10.1098/rstb.1980.0046","host_type":"publisher"},{"url":"https://royalsocietypublishing.org/rstb/article-pdf/289/1036/285/333379/rstb.1980.0046.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1098/rstb.1980.0046","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/6109324","host_type":"repository"}],"fields_of_study":["Chemical Synthesis and Analysis","Biochemical and Molecular Research","Enzyme Catalysis and Immobilization"],"mesh_terms":["Amino Acid Sequence","Binding Sites","Cephalosporins","Enzymes","Models, Chemical","Penicillins"],"keywords":["Thiazolidine","Stereochemistry","Chemistry","Active site","Binding site","Enzyme","Serine","Moiety","Residue (chemistry)","Biochemistry"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Clean water and sanitation"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-12T16:50:41.313149Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}