Structure and mechanism of non-histone protein acetyltransferase enzymes

Abstract

Post-translational modification of proteins is ubiquitous and mediates many cellular processes, including intracellular localization, protein-protein interactions, enzyme activity, transcriptional regulation and protein stability. While the role of phosphorylation as a key post-translational modification has been well studied, the more evolutionarily conserved post-translational modification acetylation has only recently attracted attention as a key regulator of cellular events. Protein acetylation has been largely studied in the context of its role in histone modification and gene regulation, where histones are modified by histone acetyltransferases to promote transcription. However, more recent acetylomic and biochemical studies have revealed that acetylation is mediated by a broader family of protein acetyltransferases. The recent structure determination of several protein acetyltransferases has provided a wealth of molecular information regarding structural features of protein acetyltransferases, their enzymatic mechanisms, their mode of substrate-specific recognition and their regulatory elements. In this review, we briefly describe what is known about non-histone protein substrates, but mainly focus on a few recent structures of protein acetyltransferases to compare and contrast them with histone acetyltransferases to better understand the molecular basis for protein recognition and modification by this family of protein modification enzymes. The structure of protein acetyltransferases (PATs) has provided molecular information on their structural features, enzymatic mechanisms, substrate-specific recognition and regulatory elements. Here, we describe non-histone protein substrates and the structure of PATs to compare and contrast them with histone acetyltransferases to better understand the molecular basis for protein recognition and modification by this burgeoning family of protein modification enzymes. © 2013. This article is a U.S. Government work and is in the public domain in the USA.