Chemical and biochemical perspectives of protein lysine methylation Journal Article


Author: Luo, M.
Article Title: Chemical and biochemical perspectives of protein lysine methylation
Abstract: Protein lysine methylation is a distinct posttranslational modification that causes minimal changes in the size and electrostatic status of lysine residues. Lysine methylation plays essential roles in regulating fates and functions of target proteins in an epigenetic manner. As a result, substrates and degrees (free versus mono/di/tri) of protein lysine methylation are orchestrated within cells by balanced activities of protein lysine methyltransferases (PKMTs) and demethylases (KDMs). Their dysregulation is often associated with neurological disorders, developmental abnormalities, or cancer. Methyllysine-containing proteins can be recognized by downstream effector proteins, which contain methyllysine reader domains, to relay their biological functions. While numerous efforts have been made to annotate biological roles of protein lysine methylation, limited work has been done to uncover mechanisms associated with this modification at a molecular or atomic level. Given distinct biophysical and biochemical properties of methyllysine, this review will focus on chemical and biochemical aspects in addition, recognition, and removal of this posttranslational mark. Chemical and biophysical methods to profile PKMT substrates will be discussed along with classification of PKMT inhibitors for accurate perturbation of methyltransferase activities. Semisynthesis of methyllysine-containing proteins will also be covered given the critical need for these reagents to unambiguously define functional roles of protein lysine methylation. © 2018 American Chemical Society.
Keywords: methylation; proteins; methyltransferases; alkylation; amino acids; biological functions; methyltransferase activity; post-translational modifications; neurological disorders; biochemical properties; biophysical methods; lysine residues
Journal Title: Chemical Reviews
Volume: 118
Issue: 14
ISSN: 0009-2665
Publisher: American Chemical Society  
Date Published: 2018-07-25
Start Page: 6656
End Page: 6705
Language: English
DOI: 10.1021/acs.chemrev.8b00008
PROVIDER: scopus
PUBMED: 29927582
PMCID: PMC6668730
DOI/URL:
Notes: Review -- Export Date: 4 September 2018 -- Source: Scopus
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  1. Minkui Luo
    70 Luo