5LKT

Crystal structure of the p300 acetyltransferase catalytic core with butyryl-coenzyme A.

5LKT の概要

• エントリーDOI: 10.2210/pdb5lkt/pdb
• 関連するPDBエントリー: 4BHW
• 分子名称: Histone acetyltransferase p300,Histone acetyltransferase p300, ZINC ION, Butyryl Coenzyme A, ... (7 entities in total)
• 機能のキーワード: p300 acetyltransferase, butyryl-coa, chromatin modification, acylation, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cytoplasm: Q09472
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 68591.82

構造登録者

Kaczmarska, Z.,Ortega, E.,Marquez, J.A.,Panne, D. (登録日: 2016-07-24, 公開日: 2016-11-02, 最終更新日: 2024-11-13)

主引用文献

Kaczmarska, Z.,Ortega, E.,Goudarzi, A.,Huang, H.,Kim, S.,Marquez, J.A.,Zhao, Y.,Khochbin, S.,Panne, D.
Structure of p300 in complex with acyl-CoA variants.
Nat. Chem. Biol., 13:21-29, 2017

PubMed Abstract: Histone acetylation plays an important role in transcriptional activation. Histones are also modified by chemically diverse acylations that are frequently deposited by p300, a transcriptional coactivator that uses a number of different acyl-CoA cofactors. Here we report that while p300 is a robust acetylase, its activity gets weaker with increasing acyl-CoA chain length. Crystal structures of p300 in complex with propionyl-, crotonyl-, or butyryl-CoA show that the aliphatic portions of these cofactors are bound in the lysine substrate-binding tunnel in a conformation that is incompatible with substrate transfer. Lysine substrate binding is predicted to remodel the acyl-CoA ligands into a conformation compatible with acyl-chain transfer. This remodeling requires that the aliphatic portion of acyl-CoA be accommodated in a hydrophobic pocket in the enzymes active site. The size of the pocket and its aliphatic nature exclude long-chain and charged acyl-CoA variants, presumably explaining the cofactor preference for p300.

PubMed: 27820805
DOI: 10.1038/nchembio.2217

実験手法

X-RAY DIFFRACTION (2.04 Å)