{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Luo Y"],"funding":["Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation)","National Natural Science Foundation of China (National Science Foundation of China)"],"pagination":["221"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11821889"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["8(1)"],"pubmed_abstract":["Histone deacetylase 8 (HDAC8) is a well-known epigenetic regulator for cancer therapy. However, developing targeted inhibitors for HDAC8 is challenging due to a limited understanding of its structural dynamics, which is crucial for ligand interaction. Here, we employed an integrated approach, including native mass spectrometry (native MS), hydrogen-deuterium exchange mass spectrometry (HDX-MS), and molecular dynamics (MD) simulation, to investigate the inhibition mechanism and dynamic regulation of human HDAC8 (hHDAC8) by selective inhibitor PCI-34051, compared with the pan-inhibitor SAHA. Our results revealed that PCI-34051 engages with an expanded set of residues and conforms more aptly to the binding channel of hHDAC8, stabilizing the flexible loops surrounding the binding channel. More"],"journal":["Communications biology"],"pubmed_title":["Binding mechanism and distant regulation of histone deacetylase 8 by PCI-34051."],"pmcid":["PMC11821889"],"funding_grant_id":["81872836","2019A1515011265","2022A1515010965","91953102"],"pubmed_authors":["Qiu Y","Li H","Yan Z","Zhang Y","Chu X","Luo Y"],"additional_accession":[]},"is_claimable":false,"name":"Binding mechanism and distant regulation of histone deacetylase 8 by PCI-34051.","description":"Histone deacetylase 8 (HDAC8) is a well-known epigenetic regulator for cancer therapy. However, developing targeted inhibitors for HDAC8 is challenging due to a limited understanding of its structural dynamics, which is crucial for ligand interaction. Here, we employed an integrated approach, including native mass spectrometry (native MS), hydrogen-deuterium exchange mass spectrometry (HDX-MS), and molecular dynamics (MD) simulation, to investigate the inhibition mechanism and dynamic regulation of human HDAC8 (hHDAC8) by selective inhibitor PCI-34051, compared with the pan-inhibitor SAHA. Our results revealed that PCI-34051 engages with an expanded set of residues and conforms more aptly to the binding channel of hHDAC8, stabilizing the flexible loops surrounding the binding channel. More","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Feb","modification":"2026-06-01T08:47:55.511Z","creation":"2025-04-07T11:26:55.436Z"},"accession":"S-EPMC11821889","cross_references":{"pubmed":["39939814"],"doi":["10.1038/s42003-025-07649-0"]}}