{"doi":"10.1101/2020.04.22.056440","title":"Mechanism of NanR gene repression and allosteric induction of bacterial sialic acid metabolism","abstract":"Abstract Bacteria respond to environmental changes by inducing transcription of some genes and repressing others. Sialic acids, which coat human cell surfaces, are a nutrient source for pathogenic and commensal bacteria. The Escherichia coli GntR-type transcriptional repressor, NanR, regulates sialic acid metabolism, but the mechanism is unclear. Here, we demonstrate that three NanR dimers bind a (GGTATA) 3 -repeat operator cooperatively and with high affinity. Truncation of an N-terminal extension abolishes cooperative binding. The effector, N -acetylneuraminate, binds NanR and attenuates DNA binding. Crystal structure data show that N -acetylneuraminate binding to NanR causes a domain rearrangement that locks the protein in a conformation that prevents DNA binding. Single-particle cryo-electron microscopy structures of NanR bound to DNA reveal the DNA binding domain is reorganized to engage DNA, while the three dimers assemble in close proximity across the (GGTATA) 3 -repeat operator allowing protein-protein interactions to form via the N-terminal extensions. Our data provides a molecular basis for the regulation of bacterial sialic acid metabolism.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":124810,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9598,"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":347611,"name":"Hariprasad Venugopal","orcid":"0000-0001-5230-2973","position":1,"is_corresponding":false},{"id":570030,"name":"Santosh Panjikar","orcid":"0000-0001-7429-3879","position":2,"is_corresponding":false},{"id":416051,"name":"Amy Henrickson","orcid":"0000-0003-3266-5202","position":3,"is_corresponding":false},{"id":381219,"name":"Emre Brookes","orcid":"0000-0001-7348-6476","position":4,"is_corresponding":false},{"id":437680,"name":"Rachel A. North","orcid":"0000-0001-5011-1567","position":5,"is_corresponding":false},{"id":285438,"name":"James M. Murphy","orcid":"0000-0003-0195-3949","position":6,"is_corresponding":false},{"id":570031,"name":"Rosmarie Friemann","orcid":"0000-0002-5633-2894","position":7,"is_corresponding":false},{"id":570032,"name":"Michael D. W. Griffin","orcid":"0000-0001-9845-7735","position":8,"is_corresponding":false},{"id":570033,"name":"Georg Ramm","orcid":"0000-0003-3596-2288","position":9,"is_corresponding":false},{"id":399433,"name":"Borries Demeler","orcid":"0000-0002-2414-9518","position":10,"is_corresponding":false},{"id":421865,"name":"Renwick C. J. Dobson","orcid":"0000-0002-5506-4939","position":11,"is_corresponding":false},{"id":421864,"name":"Christopher R. Horne","orcid":"0000-0003-1318-514X","position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":null,"created_at":"2026-07-18T23:15:11.632153Z","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":[]}