{"doi":"10.1101/2025.01.24.634716","title":"Discovery of Chirally-dependent Protein O-2-Hydroxyglutarylation by D2HG and L2HG","abstract":"Mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 are common in multiple types of human cancer, leading to the accumulation of D-2-hydroxyglutarate (D2HG) and the promotion of tumorigenesis 1 . Here we discovered a novel O -2- hydroxyglutarylation by D2HG using chemical proteomics and further revealed distinct chiral preferences for D/L2HG modifications. Notably, we identified two kinases, MRCKA and SLK, modified by D2HG and L2HG respectively, and detected reduced phosphorylation of their substrates, suggesting an inhibitory effect of D/L 2HG modifications on the kinases’ activity.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":557178,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9567,"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":[{"id":1049670,"name":"Yi‐Kai Liu","orcid":"0000-0001-8712-3326","position":1,"is_corresponding":false},{"id":993166,"name":"Zhuojun Luo","orcid":"0000-0001-6634-4090","position":2,"is_corresponding":false},{"id":1457508,"name":"Meng-Ju Wu","orcid":null,"position":3,"is_corresponding":false},{"id":1058692,"name":"Claudia N. Evans","orcid":"0009-0003-2890-3869","position":4,"is_corresponding":false},{"id":1021288,"name":"Zihan Qu","orcid":"0009-0004-8446-8459","position":5,"is_corresponding":false},{"id":946046,"name":"Fanglei Xue","orcid":"0000-0002-1848-2322","position":6,"is_corresponding":false},{"id":236994,"name":"Zhong‐Yin Zhang","orcid":"0000-0002-3234-0769","position":7,"is_corresponding":false},{"id":630681,"name":"Elizabeth I. Parkinson","orcid":"0000-0002-3665-5522","position":8,"is_corresponding":false},{"id":50927,"name":"Nabeel Bardeesy","orcid":"0000-0003-3867-0416","position":9,"is_corresponding":false},{"id":250410,"name":"W. Andy Tao","orcid":"0000-0002-5535-5517","position":10,"is_corresponding":false},{"id":1455589,"name":"Zheng Zhang","orcid":"0000-0001-9190-8900","position":0,"is_corresponding":true}],"reference_count":18,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:55:17.435961Z","pmid":"39975355","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":[]}