Commentary on: γ-enolase (ENO2) is methylated at the Nτ position of His-190 among enolase isozymes.

Post-translational modifications play crucial roles in regulating protein function. Protein methylation, occurring at lysine, arginine, and histidine, has gained attention, particularly for histone methylation. However, the mechanism and significance of protein methylation at histidine remains poorly understood. Kasai et al. developed a novel method to identify histidine-methylated proteins and discovered that γ-enolase in the mouse brain undergoes Nτ-methylation at His190. This modification reduces dimerization and enzymatic activity, suggesting this reaction plays a physiological role. This work will accelerate research on histidine methylation and help elucidate unknown phenomena in the brain.