{"doi":"10.1038/s42003-021-01683-4","title":"Crystal structure of the human PRPK–TPRKB complex","abstract":"Mutations of the p53-related protein kinase (PRPK) and TP53RK-binding protein (TPRKB) cause Galloway-Mowat syndrome (GAMOS) and are found in various human cancers. We have previously shown that small compounds targeting PRPK showed anti-cancer activity against colon and skin cancer. Here we present the 2.53 Å crystal structure of the human PRPK-TPRKB-AMPPNP (adenylyl-imidodiphosphate) complex. The structure reveals details in PRPK-AMPPNP coordination and PRPK-TPRKB interaction. PRPK appears in an active conformation, albeit lacking the conventional kinase activation loop. We constructed a structural model of the human EKC/KEOPS complex, composed of PRPK, TPRKB, OSGEP, LAGE3, and GON7. Disease mutations in PRPK and TPRKB are mapped into the structure, and we show that one mutation, PRPK K238Nfs*2, lost the binding to OSGEP. Our structure also makes the virtual screening possible and paves the way for more rational drug design.","journal":"Communications Biology","year":2021,"id":178143,"datarank":0.9519120208048398,"base_score":2.995732273553991,"endowment":2.995732273553991,"self_citation_contribution":0.4493598410330987,"citation_network_contribution":0.5025521797717412,"self_endowment_contribution":0.4493598410330987,"citer_contribution":0.5025521797717412,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":19,"citers_with_citation_signal":14,"citers_with_endowment":14,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9337,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":407506,"name":"Xinli Ma","orcid":"0000-0002-8840-2236","position":1,"is_corresponding":false},{"id":402208,"name":"Surajit Banerjee","orcid":"0000-0002-9414-7163","position":2,"is_corresponding":false},{"id":202512,"name":"Hanyong Chen","orcid":null,"position":3,"is_corresponding":false},{"id":408314,"name":"Weiya Ma","orcid":null,"position":4,"is_corresponding":false},{"id":134899,"name":"Ann M. Bode","orcid":null,"position":5,"is_corresponding":false},{"id":407510,"name":"Zigang Dong","orcid":"0000-0002-4174-4028","position":6,"is_corresponding":false},{"id":407505,"name":"Jian Li","orcid":"0000-0002-7532-1728","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:47:36.112170Z","pmid":"33547416","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":[]}