Molecular dynamics simulations indicate an induced-fit mechanism for LSD1/CoREST-H3-histone molecular recognition.

ABSTRACT:

Background

Lysine Specific Demethylase (LSD1 or KDM1A) in complex with its co-repressor protein CoREST catalyzes the demethylation of the H3 histone N-terminal tail and is currently one of the most promising epigenetic targets for drug discovery against cancer and neurodegenerative diseases. Models of non-covalent binding, such as lock and key, induced-fit, and conformational selection could help explaining the molecular mechanism of LSD1/CoREST-H3-histone association, thus guiding drug discovery and design efforts. Here, we quantify the extent to which LSD1/CoREST substrate binding is consistent with these hypothetical models using LSD1/CoREST conformational ensembles obtained through extensive explicit solvent molecular dynamics (MD) simulations.

Results

We find that an in

SUBMITTER: Vellore NA 

PROVIDER: S-EPMC4175114 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature