A rationally‐designed chimeric KDM1A/KDM1B histone demethylase tower domain deletion mutant retaining enzymatic activity | Zendy

Burg Jonathan M. | Zendy; Makhoul Alan T. | Zendy; Pemble Charles W. | Zendy; Link Jennifer E. | Zendy; Heller Frederick J. | Zendy; McCafferty Dewey G. | Zendy

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

Author(s) -

Burg Jonathan M.,

Makhoul Alan T.,

Pemble Charles W.,

Link Jennifer E.,

Heller Frederick J.,

McCafferty Dewey G.

Publication year - 2015

Publication title -

febs letters

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.593

H-Index - 257

eISSN - 1873-3468

pISSN - 0014-5793

DOI - 10.1016/j.febslet.2015.07.028

Subject(s) - demethylase , corepressor , mutant , microbiology and biotechnology , histone , biology , chemistry , transcription factor , biochemistry , gene , repressor

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 nΔ150 KDM1AΔTower KDM1B chimera (chKDM1AΔTower), 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 chKDM1AΔTower useful for dissecting molecular contributions to KDM1A function.

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