6RXR

Crystal structure of CobB Ac2 (A76G, I131C, V162G) in complex with H4K16Cr-2'OH-ADPr peptide intermediate after co-crystallisation

6RXR の概要

• エントリーDOI: 10.2210/pdb6rxr/pdb
• 分子名称: NAD-dependent protein deacylase, Histone H4, [[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl] [(2~{R},3~{R},4~{R},5~{S})-4-[(~{E})-but-2-enoxy]-3,5-bis(oxidanyl)oxolan-2-yl]methyl hydrogen phosphate, ... (4 entities in total)
• 機能のキーワード: deacylase, nad-dependent, hydrolase
• 由来する生物種: Escherichia coli (strain K12); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 119750.59

構造登録者

Spinck, M.,Gasper, R.,Neumann, H. (登録日: 2019-06-08, 公開日: 2020-04-15, 最終更新日: 2024-11-13)

主引用文献

Spinck, M.,Neumann-Staubitz, P.,Ecke, M.,Gasper, R.,Neumann, H.
Evolved, Selective Erasers of Distinct Lysine Acylations.
Angew.Chem.Int.Ed.Engl., 59:11142-11149, 2020

PubMed Abstract: Lysine acylations, a family of diverse protein modifications varying in acyl-group length, charge, and saturation, are linked to many important physiological processes. Only a small set of substrate-promiscuous lysine acetyltransferases and deacetylases (KDACs) install and remove this vast variety of modifications. Engineered KDACs that remove only one type of acylation would help to dissect the different contributions of distinct acylations. We developed a bacterial selection system for the directed evolution of KDACs and identified variants up to 400 times more selective for butyryl-lysine compared to crotonyl-lysine. Structural analyses revealed that the enzyme adopts different conformational states depending on the type of acylation of the bound peptide. We used the butyryl-selective KDAC variant to shift the cellular acylation spectrum towards increased lysine crotonylation. These new enzymes will help in dissecting the roles of different lysine acylations in cell physiology.

PubMed: 32187803
DOI: 10.1002/anie.202002899

実験手法

X-RAY DIFFRACTION (1.7 Å)