{"doi":"10.1042/bj3430697","title":"A novel chaperone-activity-reducing mechanism of the 90-kDa molecular chaperone HSP90","abstract":"<jats:p>The 90-kDa heat shock protein (HSP90) acts as a specific molecular chaperone in the folding and regulates a wide range of associated proteins such as steroid hormone receptors. It is known that HSP90 possesses two different chaperone sites, both in the N- and C-domains, and that the chaperone activity of HSP90 is blocked by binding of geldanamycin (GA) to the N-domain, the same as the ATP-binding site. Here we show that Cisplatin [cis-diamminedichloroplatinum (II), CDDP], an antineoplastic agent, associates with HSP90 and reduces its chaperone activity. In order to analyse the binding proteins, bovine brain cytosols were applied to a CDDP-affinity column and binding proteins were eluted by CDDP. In the elutants, only 90-kDa protein bands were detected on SDS/PAGE, and the protein was cross-reacted with the anti-HSP90 antibody on immunoblotting. No protein bands were detected in the elutants from the control column on SDS/PAGE. These results indicated that CDDP has a high affinity for HSP90. On CD spectrum analysis, the binding of CDDP to HSP90 resulted in a conformational change in the protein. Although HSP90 inhibited the aggregation of citrate synthase as a molecular chaperone in vitro,the activity was suppressed almost completely in the presence of CDDP. Mg/ATP has an influence on the chaperone activity to some extent. The CDDP binding region of HSP90 is near the C-terminal which is quite different from the GA-binding site. Our results suggest that the chaperone activity of HSP90 may be inhibited by the binding of CDDP or GA by different mechanisms.</jats:p>","journal":"Biochemical Journal","year":1999,"id":22761,"datarank":3.735008845734512,"base_score":4.356708826689592,"endowment":4.356708826689592,"self_citation_contribution":0.6535063240034389,"citation_network_contribution":3.081502521731073,"self_endowment_contribution":0.6535063240034389,"citer_contribution":3.081502521731073,"corpus_percentile":null,"corpus_rank":null,"citation_count":77,"citer_count":68,"citers_with_citation_signal":63,"citers_with_endowment":63,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":142048,"name":"Masahito OGURA","orcid":null,"position":1,"is_corresponding":false},{"id":142049,"name":"Atsushi KOMATSUDA","orcid":null,"position":2,"is_corresponding":false},{"id":142050,"name":"Hideki WAKUI","orcid":null,"position":3,"is_corresponding":false},{"id":142051,"name":"Akira B. MIURA","orcid":null,"position":4,"is_corresponding":false},{"id":142052,"name":"Yohtalou TASHIMA","orcid":null,"position":5,"is_corresponding":false},{"id":142047,"name":"Hideaki ITOH","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.356708826689592,"endowment":4.356708826689592,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"10527951","pmcid":"PMC1220604","openalex_id":"https://openalex.org/W2114173273","authors":[],"funders":[],"total_grants":0,"fwci":1.6525,"citation_percentile":0.83681106,"influential_citations":0,"citation_trend":[{"year":2012,"count":2},{"year":2013,"count":2},{"year":2014,"count":1},{"year":2015,"count":2},{"year":2016,"count":2},{"year":2017,"count":3},{"year":2018,"count":2},{"year":2019,"count":1},{"year":2020,"count":1},{"year":2022,"count":1},{"year":2024,"count":1}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1220604","host_type":"repository"},{"url":"https://europepmc.org/articles/pmc1220604?pdf=render","host_type":"GREEN"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1220604","host_type":"repository"},{"url":"https://portlandpress.com/biochemj/article-pdf/343/3/697/636023/bj3430697.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1042/bj3430697","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/10527951","host_type":"repository"}],"fields_of_study":["Heat shock proteins research","Biochemical effects in animals","Biology","Medicine","Chemistry"],"mesh_terms":["Adenosine Triphosphate","Amino Acid Sequence","Animals","Binding Sites","Brain","Cattle","Chromatography, Affinity","Circular Dichroism","Cisplatin","Electrophoresis, Polyacrylamide Gel","Molecular Sequence Data","Peptide Fragments","Protein Conformation","Quinones","Benzoquinones","Protein Folding","HSP90 Heat-Shock Proteins","Lactams, Macrocyclic"],"keywords":["Hsp90","Geldanamycin","Chaperone (clinical)","Heat shock protein","Biochemistry","Binding site","Chemistry","CDC37","Protein folding","Biology"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-07T16:02:53.317854Z","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":[]}