{"doi":"10.3390/ijms232213966","title":"Insight into the Spatial Arrangement of the Lysine Tyrosylquinone and Cu2+ in the Active Site of Lysyl Oxidase-like 2","abstract":"Lysyl oxidase-2 (LOXL2) is a Cu2+ and lysine tyrosylquinone (LTQ)-dependent amine oxidase that catalyzes the oxidative deamination of peptidyl lysine and hydroxylysine residues to promote crosslinking of extracellular matrix proteins. LTQ is post-translationally derived from Lys653 and Tyr689, but its biogenesis mechanism remains still elusive. A 2.4 Å Zn2+-bound precursor structure lacking LTQ (PDB:5ZE3) has become available, where Lys653 and Tyr689 are 16.6 Å apart, thus a substantial conformational rearrangement is expected to take place for LTQ biogenesis. However, we have recently shown that the overall structures of the precursor (no LTQ) and the mature (LTQ-containing) LOXL2s are very similar and disulfide bonds are conserved. In this study, we aim to gain insights into the spatial arrangement of LTQ and the active site Cu2+ in the mature LOXL2 using a recombinant LOXL2 that is inhibited by 2-hydrazinopyridine (2HP). Comparative UV-vis and resonance Raman spectroscopic studies of the 2HP-inhibited LOXL2 and the corresponding model compounds and an EPR study of the latter support that 2HP-modified LTQ serves as a tridentate ligand to the active site Cu2. We propose that LTQ resides within 2.9 Å of the active site of Cu2+ in the mature LOXL2, and both LTQ and Cu2+ are solvent-exposed.","journal":"International Journal of Molecular Sciences","year":2022,"id":274643,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.96,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":891876,"name":"Hee-Jung Moon","orcid":"0000-0001-5409-4418","position":1,"is_corresponding":false},{"id":719340,"name":"Sinan Sabuncu","orcid":"0000-0001-8346-8175","position":2,"is_corresponding":false},{"id":943183,"name":"Priya Singh","orcid":"0000-0002-2499-3137","position":3,"is_corresponding":false},{"id":361196,"name":"Trey A. Ronnebaum","orcid":"0000-0002-9214-3564","position":4,"is_corresponding":false},{"id":943184,"name":"Siyu Ou","orcid":"0000-0001-7544-8131","position":5,"is_corresponding":false},{"id":740902,"name":"Justin T. Douglas","orcid":"0000-0002-7901-184X","position":6,"is_corresponding":false},{"id":475821,"name":"Timothy A. Jackson","orcid":"0000-0002-3529-2715","position":7,"is_corresponding":false},{"id":588284,"name":"Pierre Moënne‐Loccoz","orcid":"0000-0002-7684-7617","position":8,"is_corresponding":false},{"id":763330,"name":"Minae Mure","orcid":"0000-0001-6768-7810","position":9,"is_corresponding":false},{"id":920697,"name":"Alex Meier","orcid":"0000-0003-3077-6232","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-19T00:28:12.324621Z","pmid":"36430446","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":[]}