{"doi":"10.17615/qe7c-h860","title":"Structure of the nociceptin/orphanin FQ receptor in complex with a peptide mimetic","abstract":"Members of the Opioid Receptor (OR) family of G protein-coupled receptors (GPCRs) are found throughout the peripheral and central nervous system where they play key roles in nociception and analgesia. Unlike the classical ORs, δ–OR, κ–OR,1 and μ-OR,2 which were delineated by pharmacological criteria in the 1970’s and 1980’s, the nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP, aka ORL-1) was discovered relatively recently via molecular cloning and characterization of an orphan GPCR3. Despite its high sequence similarity (~60%) with ORs, NOP has a strikingly distinct pharmacology4,5. Despite high sequence similarity with classical opioid G protein-coupled receptor subtypes, the nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP) has a distinct biological and pharmacological role, featuring activation by the endogenous peptide N/OFQ, and unique selectivity for exogenous ligands. This study reports the crystal structure of human NOP solved in complex with the peptide mimetic antagonist Banyu Compound-24 (C-24), revealing atomic details of ligand-receptor recognition and selectivity. C-24 mimics the first four N-terminal residues of the NOP-selective peptide antagonist UFP-101, a close derivative of N/OFQ, and provides important clues to binding of these peptides. The X-ray structure also reveals substantial conformational differences in the pocket regions between NOP and the “classical” opioid receptors κ (Ref. 1) and μ (Ref. 2), which are likely due to a small number of residues that vary between the two receptors. The NOP/C-24 structure explains the divergent selectivity profile of NOP and provides a new structural template for the design of NOP ligands.","journal":"UNC Libraries","year":2020,"id":144377,"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":0.9629,"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":612867,"name":"Claudio Trapella","orcid":"0000-0002-6666-143X","position":1,"is_corresponding":false},{"id":198890,"name":"Vadim Cherezov","orcid":"0000-0002-5265-3914","position":2,"is_corresponding":false},{"id":40489,"name":"Vsevolod Katritch","orcid":"0000-0003-3883-4505","position":3,"is_corresponding":false},{"id":103670,"name":"Xi‐Ping Huang","orcid":"0000-0002-2585-653X","position":4,"is_corresponding":false},{"id":613455,"name":"Eugene Chun","orcid":null,"position":5,"is_corresponding":false},{"id":444598,"name":"Eyal Vardy","orcid":null,"position":6,"is_corresponding":false},{"id":225473,"name":"Bryan L. Roth","orcid":"0000-0002-0561-6520","position":7,"is_corresponding":false},{"id":411024,"name":"Wei Liu","orcid":"0000-0002-1727-6738","position":8,"is_corresponding":false},{"id":612868,"name":"Girolamo Calò","orcid":"0000-0001-5436-959X","position":9,"is_corresponding":false},{"id":612869,"name":"Remo Guerrini","orcid":"0000-0002-7619-0918","position":10,"is_corresponding":false},{"id":266181,"name":"Raymond C. Stevens","orcid":"0000-0002-4522-8725","position":11,"is_corresponding":false},{"id":608963,"name":"Aaron A. Thompson","orcid":"0000-0003-4314-4242","position":12,"is_corresponding":false},{"id":443708,"name":"Huixian Wu","orcid":"0009-0003-9112-3224","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:17:45.339291Z","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":[]}