Unraveling the Catalytic Mechanism and Substrate Selectivity of HDAC10: A Dual-Filter Approach for Polyamine Deacetylation.

ABSTRACT: The histone deacetylase (HDAC) family plays a crucial role in regulating acetylation-dependent cellular processes, with dysregulation linked to diseases ranging from cancer to neurodegeneration. HDAC10, the sole polyamine deacetylase in the HDAC family, uniquely influences pathologies such as tumor immunity, autophagy, inflammation, virus infection, silicosis, etc. Despite its therapeutic potential, the molecular basis of HDAC10's catalytic activity and substrate selectivity remains poorly understood, hindering rational drug design. Here, we address this gap by integrating density functional theory (DFT) and molecular dynamics simulation to systematically investigate HDAC10's catalytic activity and substrate selectivity. Utilizing a 330-atom quantum cluster model, we evaluated five

SUBMITTER: Cai S 

PROVIDER: S-EPMC12458008 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature