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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Burg, JM; Makhoul, AT; Pemble, CW; Link, JE; Heller, FJ; McCafferty, DG

Published Date

  • August 2015

Published In

Volume / Issue

  • 589 / 18

Start / End Page

  • 2340 - 2346

PubMed ID

  • 26226427

Electronic International Standard Serial Number (EISSN)

  • 1873-3468

International Standard Serial Number (ISSN)

  • 0014-5793

Digital Object Identifier (DOI)

  • 10.1016/j.febslet.2015.07.028

Language

  • eng