Catalytic mechanism of histone acetyltransferase p300: from the proton transfer to acetylation reaction.

ABSTRACT: The transcriptional coactivator and histone acetyltransferase (HAT) p300 acetylates the four core histones and other transcription factors to regulate a plethora of fundamental biological processes including cell growth, development, oncogenesis and apoptosis. Recent structural and biochemical studies on the p300 HAT domain revealed a Theorell-Chance, or "hit-and-run", catalytic mechanism. Nonetheless, the chemical mechanism of the entire reaction process including the proton transfer (PT) scheme and consequent acetylation reaction route remains unclear. In this study, a combined computational strategy consisting of molecular modeling, molecular dynamic (MD) simulation, and quantum mechanics/molecular mechanics (QM/MM) simulation was applied to elucidate these important issues. An initial

SUBMITTER: Zhang X 

PROVIDER: S-EPMC4037238 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature