A rationally-designed chimeric KDM1A/KDM1B histone demethylase tower domain deletion mutant retaining enzymatic activity.

ABSTRACT: A target with therapeutic potential, lysine-specific demethylase 1A (KDM1A) is a regulator of gene expression whose tower domain is a protein-protein interaction motif. This domain facilitates the interaction of KDM1A with coregulators and multiprotein complexes that direct its activity to nucleosomes. We describe the design and characterization of a chimeric 'towerless' KDM1A, termed n?150 KDM1A?Tower KDM1B chimera (chKDM1A?Tower), which incorporates a region from the paralog lysine-specific demethylase 1B (KDM1B). This chimera copurifies with FAD and displays demethylase activity, but fails to bind the partner protein corepressor of the RE1-silencing transcription factor (CoREST). We conclude that KDM1A catalysis can be decoupled from tower-dependent interactions, lending chKDM1A?Tower useful for dissecting molecular contributions to KDM1A function.

SUBMITTER: Burg JM 

PROVIDER: S-EPMC4806859 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature