A computational insight into the interaction of methylated lysines with aromatic amino acid cages

Abstract

Posttranslational lysine methylations in histone proteins are recognized by specific reader proteins. The interaction proceeds through the binding of methylated lysine to the aromatic cages created by the combinations of tryptophan and/or tyrosine and/or phenylalanine, and it is specific to the degree of methylation of lysine residue. The chemical recognition is based on cation‐π interaction between positively charged lysine and the π system of the aromatic groups. In this study, the energetics of the binding of model methylated Lys to the model aromatic amino acids as well as aromatic cages are investigated with density functional theory calculations. Molecular orbitals corresponding to the bound complexes and separate lysine and aromatic amino acid components are analyzed. Finally, using single‐point energy calculations, the feasibility of comparing binding energies/affinities of methylated lysines with different methylation degrees is shown, using available crystal structures of the bound model complexes.

Comparative Computational Approach To Study Enzyme Reactions Using QM and QM-MM Methods

“…It is visible that the negatively charged Glu312 is in close proximity to glycine betaine’s positively charged tetrasubstituted N atom, suggesting that an electrostatic interaction between choline and this residue might exist during the hydride-transfer process. Moreover, the tetramethyl ammonium portion of the glycine betaine faces Trp331 closely, and this interaction is very similar to cation−π interaction occurring between tetramethylated lysines and aromatic amino acids . Another observation is that Tyr465 is in close proximity to methyl groups on FAD and choline, and this suggests possible van der Waals interactions.…”

“…Moreover, the tetramethyl ammonium portion of the glycine betaine faces Trp331 closely, and this interaction is very similar to cation−π interaction occurring between tetramethylated lysines and aromatic amino acids. 42 Another observation is that Tyr465 is in close proximity to methyl groups on FAD and choline, and this suggests possible van der Waals interactions.…”

Structural Assessment and Catalytic Oxidation Activity of Hydrophobized Whey Proteins

“…Cation−π attractive interactions between lysine residues and aromatic cages formed by the benzene rings of tryptophan, tyrosine, and phenylalanine are known to be prerequisites for the recognition of posttranslationally methylated lysines in histone proteins by specific reader proteins. 57 Moreover, such cation−π interactions drive the self-assembly of simple aromatic-and lysinerich peptides. 58 We argue that comparable cation−π interactions happened between free amino groups of whey proteins and the benzene rings of hydroquinone derivatives, such as semiquinone radicals, facilitating radical stabilization and inter-radical reactions.…”

“…It is suggested that free amino groups play an important role in the catalytic properties of whey proteins. Cation−π attractive interactions between lysine residues and aromatic cages formed by the benzene rings of tryptophan, tyrosine, and phenylalanine are known to be prerequisites for the recognition of post-translationally methylated lysines in histone proteins by specific reader proteins . Moreover, such cation−π interactions drive the self-assembly of simple aromatic- and lysine-rich peptides .…”

Bi-terminal fusion of intrinsically-disordered mussel foot protein fragments boosts mechanical strength for protein fibers

“…The dominant form of interaction between Mfp5 are cation-π interaction (Y-K/R) 20,35,36 and π-π stacking (Y-Y) 37 . Previous research mostly emphasized the former and estimated a binding energy of −20.8 kcal/mol per Y-K pair 38 . More recently, ab initio quantum mechanical simulation suggested that total binding energy from π-π stacking can add up to 33-50% of the cation-π interactions 36 .…”