{"doi":"10.1101/2020.06.01.126664","title":"Molecular Bases of the Membrane Association Mechanism Potentiating Antibiotic Resistance by New Delhi Metallo- <i>β</i> -Lactamase 1","abstract":"ABSTRACT Resistance to last-resort carbapenem antibiotics is an increasing threat to human health, as it critically limits therapeutic options. Metallo- β -lactamases are the largest family of carbapenemases, enzymes that inactivate these drugs. Among MBLs, New Delhi metallo- β -lactamase 1 has experienced the fastest and largest worldwide dissemination. This success has been attributed to the fact that NDM-1 is a lipidated protein anchored to the outer membrane of bacteria, while all other MBLs are soluble periplasmic enzymes. By means of a combined experimental and computational approach, we show that NDM-1 interacts with the surface of bacterial membranes in a stable, defined conformation, in which the active site is not occluded by the bilayer. Although the lipidation is required for a long-lasting interaction, the globular domain of NDM-1 is tuned to interact specifically with the outer bacterial membrane. In contrast, this affinity is not observed for VIM-2, a natively soluble MBL. Finally, we identify key residues involved in the membrane interaction of NDM-1, which constitute potential targets for developing therapeutic strategies able to combat resistance granted by this enzyme.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":126779,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9529,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":574732,"name":"Guillermo Bahr","orcid":"0000-0003-2187-4463","position":1,"is_corresponding":false},{"id":409934,"name":"Lisandro J. González","orcid":"0000-0002-0575-1810","position":2,"is_corresponding":false},{"id":306839,"name":"Alejandro J. Vila","orcid":"0000-0002-7978-3233","position":3,"is_corresponding":false},{"id":464256,"name":"Matteo Dal Peraro","orcid":"0000-0002-2973-3975","position":4,"is_corresponding":false},{"id":574731,"name":"Alessio Prunotto","orcid":"0000-0002-6425-964X","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-18T23:15:27.226519Z","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":[]}