{"doi":"10.1073/pnas.2101989118","title":"Cleavage of Braun’s lipoprotein Lpp from the bacterial peptidoglycan by a paralog of\n                    <scp>l</scp>\n                    ,\n                    <scp>d</scp>\n                    -transpeptidases, LdtF","abstract":"<jats:title>Significance</jats:title>\n                  <jats:p>\n                    Bacterial cell walls contain a protective exoskeleton, peptidoglycan, which is a target of several clinically important antimicrobials. In gram-negative bacteria, peptidoglycan is covered by an additional lipid layer, outer membrane, that serves as a permeability barrier against the entry of toxic molecules. In some bacteria, an abundant lipoprotein, Lpp, staples the outer membrane to peptidoglycan to maintain the structural integrity of the cell envelope. In this study, we identify a previously unknown hydrolytic enzyme that cleaves Lpp from the peptidoglycan and show how the outer membrane–peptidoglycan linkages are modulated in\n                    <jats:italic>Escherichia coli</jats:italic>\n                    . Overall, this study helps in understanding the fundamental bacterial cell wall biology and in the identification of alternate drug targets for the development of new antimicrobials.\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2021,"id":596443,"datarank":0.5641800173540344,"base_score":3.7612001156935624,"endowment":3.7612001156935624,"self_citation_contribution":0.5641800173540344,"citation_network_contribution":0.0,"self_endowment_contribution":0.5641800173540344,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":42,"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":1178611,"name":"Pavan Kumar Chodisetti","orcid":"0000-0002-4890-8531","position":1,"is_corresponding":false},{"id":1527566,"name":"Manjula Reddy","orcid":null,"position":2,"is_corresponding":false},{"id":1527563,"name":"Raj Bahadur","orcid":"0000-0002-4673-6844","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Cleavage of Braun's lipoprotein Lpp from the bacterial peptidoglycan by a paralog of l,d-transpeptidases, LdtF.","abstract":"The gram-negative bacterial cell envelope is made up of an outer membrane (OM), an inner membrane (IM) that surrounds the cytoplasm, and a periplasmic space between the two membranes containing peptidoglycan (PG or murein). PG is an elastic polymer that forms a mesh-like sacculus around the IM, protecting cells from turgor and environmental stress conditions. In several bacteria, including <i>Escherichia coli</i>, the OM is tethered to PG by an abundant OM lipoprotein, Lpp (or Braun's lipoprotein), that functions to maintain the structural and functional integrity of the cell envelope. Since its discovery, Lpp has been studied extensively, and although l,d-transpeptidases, the enzymes that catalyze the formation of PG-Lpp linkages, have been earlier identified, it is not known how these linkages are modulated. Here, using genetic and biochemical approaches, we show that LdtF (formerly <i>yafK</i>), a newly identified paralog of l,d-transpeptidases in <i>E. coli</i>, is a murein hydrolytic enzyme that catalyzes cleavage of Lpp from the PG sacculus. LdtF also exhibits glycine-specific carboxypeptidase activity on muropeptides containing a terminal glycine residue. LdtF was earlier presumed to be an l,d-transpeptidase; however, our results show that it is indeed an l,d-endopeptidase that hydrolyzes the products generated by the l,d-transpeptidases. To summarize, this study describes the discovery of a murein endopeptidase with a hitherto unknown catalytic specificity that removes the PG-Lpp cross-links, suggesting a role for LdtF in the regulation of PG-OM linkages to maintain the structural integrity of the bacterial cell envelope.","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"33941679","pmcid":"PMC8126863","openalex_id":null,"authors":[],"funders":[{"funder_name":"Department of Biotechnology , Ministry of Science and Technology","grant_id":"BT/01/COE/07/02-II","title":null},{"funder_name":"Council of Scientific and Industrial Research","grant_id":"MLP0141","title":null}],"total_grants":2,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://www.pnas.org/content/pnas/118/19/e2101989118.full.pdf","host_type":"publisher"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8126863","host_type":"repository"}],"fields_of_study":[],"mesh_terms":["Escherichia coli","Cysteine Endopeptidases","Carboxypeptidases","Peptidyl Transferases","Peptidoglycan","Lipoproteins","Glycine","Bacterial Outer Membrane Proteins","Escherichia coli Proteins","Chromatography, High Pressure Liquid","Mutation","Mass Spectrometry"],"keywords":["peptidoglycan","Bacterial Cell Wall","Lpp","Ldtf"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-28T10:15:14.615080Z","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":[]}