Modelling the Full-Length Inactive PKC-δ Structure to Explore Regulatory Accessibility and Selective Targeting Opportunities.

ABSTRACT: Background/Objectives: Protein kinase C-δ (PKC-δ) is a pivotal regulator of cellular signalling, and its dysregulation contributes to oncogenesis. While certain isolated PKC-δ domains have been crystallised, the full-length architecture and interdomain interactions remain largely unresolved, limiting mechanistic insight and the design of selective modulators. We aimed to define the full-length, inactive conformation of PKC-δ and identify accessible, functionally relevant binding sites for ligand discovery. Methods: We generated a consensus structural model of full-length inactive PKC-δ using multi-template comparative modelling guided by established inactivity markers. Molecular docking was used to predict ligands targeting the C2 domain, which were subsequently validated in

SUBMITTER: Khader R 

PROVIDER: S-EPMC12655620 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature