{"doi":"10.1101/2020.11.19.389957","title":"Ribonucleotide reductase, a novel target for gonorrhea","abstract":"Abstract Antibiotic resistant Neisseria gonorrhoeae (Ng) are an emerging public health threat due to increasing numbers of multidrug resistant (MDR) organisms. We identified two novel orally active inhibitors, PTC-847 and PTC-672, that exhibit a narrow spectrum of activity against Ng including MDR isolates. By selecting organisms resistant to the novel inhibitors and sequencing their genomes, we identified a new therapeutic target, the class Ia ribonucleotide reductase (RNR). Activity studies and negative stain electron microscopy of the Ng Ia RNR suggest that these inhibitors potentiate conversion of its active α 2 β 2 state to an inactive α 4 β 4 similar to states first identified with the Escherichia coli (Ec) Ia RNR. Resistance mutations in Ng map to the N -terminal, ATP cone domain of its α subunit and disrupt the interaction with the β subunit required to form the specific quaternary inhibited state. Oral administration of PTC-672 reduces Ng infection in a mouse model and may have therapeutic potential for treatment of Ng that is resistant to current drugs.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":125600,"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":0.9606,"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":573035,"name":"Suzanne Letinski","orcid":null,"position":1,"is_corresponding":false},{"id":572264,"name":"Stephen P. Jung","orcid":"0000-0002-9276-175X","position":2,"is_corresponding":false},{"id":573036,"name":"Aleksey I. Gerasyuto","orcid":null,"position":3,"is_corresponding":false},{"id":453009,"name":"J. Wang","orcid":"0009-0004-9223-8493","position":4,"is_corresponding":false},{"id":572265,"name":"Michael Arnold","orcid":"0000-0002-2560-9360","position":5,"is_corresponding":false},{"id":90805,"name":"G. Chen","orcid":null,"position":6,"is_corresponding":false},{"id":573037,"name":"Jean Hedrick","orcid":null,"position":7,"is_corresponding":false},{"id":573038,"name":"Melissa Dumble","orcid":null,"position":8,"is_corresponding":false},{"id":573039,"name":"Kanchana Ravichandran","orcid":null,"position":9,"is_corresponding":false},{"id":572266,"name":"Talya S. Levitz","orcid":"0000-0001-9938-7580","position":10,"is_corresponding":false},{"id":240330,"name":"Christopher J. Chang","orcid":"0000-0001-5732-9497","position":11,"is_corresponding":false},{"id":241330,"name":"Catherine L. Drennan","orcid":"0000-0001-5486-2755","position":12,"is_corresponding":false},{"id":573040,"name":"J. Stubbe","orcid":null,"position":13,"is_corresponding":false},{"id":561099,"name":"Gary M. Karp","orcid":null,"position":14,"is_corresponding":false},{"id":572267,"name":"Arthur Branstrom","orcid":"0000-0002-5917-6372","position":15,"is_corresponding":false},{"id":572263,"name":"Jana Narasimhan","orcid":"0000-0001-5621-8592","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-18T23:15:19.482428Z","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":[]}