Approximately 2000 structures of methyltransferases (MTases) are currently available, displaying fifteen different folds for binding a methyl donor and providing molecular level insight into nearly half the human methyltransferome. Several MTases involved in gene expression and regulation are catalytically inefficient when isolated, and their catalytic domains often show inhibitory active site architectures. Recently reported structures of complexes that more closely reflect biological context have begun to reveal the structural basis of activation. DNA and particular histone MTases are allosterically activated by binding histone modifications using reader domains or separate reader proteins, and some MTases operating beyond chromatin are activated by binding an activator protein. In this review, we describe the structural status of the human methyltransferome and then discuss newly revealed structural mechanisms of MTase activation.
Copyright © 2018. Published by Elsevier Ltd.