Nonenzymatic acetylation of ubiquitin Lys side chains is modulated by their neighboring residues

Nonenzymatic acetylation of Lys side chains (Lys‐SCs) by various in vivo reactive molecules has been suggested to play novel regulatory roles. Ubiquitin (UB) has seven Lys residues that are utilized for synthesis of specific poly‐UB chains. To understand the nature of these Lys‐SC modifications, the...

Full description

Saved in:
Bibliographic Details
Published in:The FEBS journal 2018-04, Vol.285 (7), p.1277-1289
Main Authors: Lee, Seo‐Yeon, Choi, Yun‐Seok, Kim, Eun‐Hee, Cheong, Hae‐Kap, Lee, Yun‐Ju, Lee, Jin‐Gu, Ye, Yihong, Ryu, Kyoung‐Seok
Format: Article
Language:English
Subjects:
2‐acetylthio acetamide
Acetylation
Catalysis
Catalytic activity
Chains
Chemical properties
Energy measurement
Mutagenesis
NMR
nonenzymatic acetylation
Nuclear magnetic resonance
Proteins
Residues
Ubiquitin
ubiquitin Lys pKa
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Nonenzymatic acetylation of Lys side chains (Lys‐SCs) by various in vivo reactive molecules has been suggested to play novel regulatory roles. Ubiquitin (UB) has seven Lys residues that are utilized for synthesis of specific poly‐UB chains. To understand the nature of these Lys‐SC modifications, the chemical acetylation rate and pKa and Hill coefficient of each UB‐Lys‐SC were measured. Mutagenesis studies combined with the determination of activation energy indicated that specific neighboring residues of the Lys‐SCs have a potential catalytic activity during nonenzymatic acetylation. Based on the shared chemistry between nonenzymatic Lys acetylation and ubiquitylation, the characterized chemical properties of the UB‐Lys‐SCs could be a reference for deciphering both mechanisms. Our NMR approaches could be useful for studying general nonenzymatic Lys acylations of various proteins. To understand the nature of dynamic ubiquitin Lys side chain (UB‐Lys‐SC) modifications, nonenzymatic Lys‐acetylation and ubiquitylation, the chemical acetylation rate by 2‐(acetylthio)acetamide and the pKa and Hill coefficient of each UB‐Lys‐SC were measured by NMR. Mutagenesis studies combined with the determination of activation energy indicated that specific neighboring residues of the UB‐Lys‐SCs have a potential catalytic activity during nonenzymatic acetylation.
ISSN:1742-464X
1742-4658
DOI:10.1111/febs.14404