{"doi":"10.1002/pro.70288","title":"Poster Session I","abstract":"-lactam antibiotics are one of the most important and widely used antibiotic classes for treating many infectious diseases.Since the discovery of -lactam antibiotics, bacteria have conferred resistance to them through the development of antibiotic-modifying enzymes, -lactamases.Metallo--lactamase enzymes are a type of -lactamase that require zinc ions to catalyze the hydrolysis of the -lactam ring, rendering antibiotics like cephalexin ineffective.Cephalexin, also known as Keflex, is a cephalosporin class -lactam antibiotic used to treat many diseases like gonorrhea and skin infections.However, it is vulnerable to hydrolysis by metallo-lactamases like New Delhi Metallo--lactamase-4 (NDM-4), found in Klebsiella pneumoniae.We used highthroughput virtual screening to identify tentative inhibitors that potentially shut down NDM-4 -lactamase function.Then we evaluated the potential inhibitors by UV-Vis kinetics and x-ray crystallography using cephalexin as the substrate.Structural insights gained through x-ray crystallography are combined with the kinetic data to provide important structure-function relationships between active site residues, zinc ions, and the inhibitors.Our preliminary kinetics and crystallographic efforts lay the foundation for future investigations into NDM-4 inhibition.Ongoing work will combine structural and functional insights to inform the design of more potent inhibitors.","journal":"Protein Science","year":2025,"id":583359,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.952,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:59:03.725721Z","pmid":"41307477","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":[]}