Exploration of the Activation Mechanism of the Epigenetic Regulator MLL3: A QM/MM Study.

ABSTRACT: The mixed lineage leukemia 3 or MLL3 is the enzyme in charge of the writing of an epigenetic mark through the methylation of lysine 4 from the N-terminal domain of histone 3 and its deregulation has been related to several cancer lines. An interesting feature of this enzyme comes from its regulation mechanism, which involves its binding to an activating dimer before it can be catalytically functional. Once the trimer is formed, the reaction mechanism proceeds through the deprotonation of the lysine followed by the methyl-transfer reaction. Here we present a detailed exploration of the activation mechanism through a QM/MM approach focusing on both steps of the reaction, aiming to provide new insights into the deprotonation process and the role of the catalytic machinery in the methyl-transf

SUBMITTER: Miranda-Rojas S 

PROVIDER: S-EPMC8301819 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature