8IYO

Crystal structure of a protein acetyltransferase, HP0935, acetyl-CoA bound form

8IYO の概要

• エントリーDOI: 10.2210/pdb8iyo/pdb
• 関連するPDBエントリー: 8IYM
• 分子名称: N-acetyltransferase domain-containing protein, ACETYL COENZYME *A (3 entities in total)
• 機能のキーワード: gnat domain, protein acetyltransferase, acetyl-coenzyme a, transferase
• 由来する生物種: Helicobacter pylori 26695
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 77744.30

構造登録者

Dadireddy, V.,Mahanta, P.,Kumar, A.,Desirazu, R.N.,Ramakumar, S. (登録日: 2023-04-05, 公開日: 2024-04-10, 最終更新日: 2025-07-30)

主引用文献

Dadireddy, V.,Kumar, A.,Kumar, S.,Sarma, S.P.,Mahanta, P.,Ramakumar, S.,Desirazu, R.N.
Biochemical and structural characterization of a GNAT superfamily protein acetyltransferase from Helicobacter pylori.
J.Biol.Chem., 301:110356-110356, 2025

PubMed Abstract: Helicobacter pylori (H. pylori), a gastric pathogen with high genetic variability and a unique niche, causes peptic ulcers and gastric cancer. Natural transformation contributes to the genetic variability of H. pylori. To date, protein acetylation and the associated acetyltransferase(s) have not been reported in this bacterium. Here, we report protein acetylation in H. pylori and identify a putative protein acetyltransferase, HP0935, capable of acetylating amino acids and proteins, including DNA processing protein A (DprA), which is involved in natural transformation. HP0935 acetylates residue K133 in DprA, which is important for DNA binding, thus is likely to regulate natural transformation. We determined the crystal structures of HP0935 in its apo form and in complex with acetyl-coenzyme A (ACO) to 2.00 Å and 2.40 Å resolution, respectively. Structural analysis revealed a conformational change in the substrate-binding loops, α1-α2 and β6-β7, upon ACO binding. The structural comparison showed that HP0935 differs from other protein acetyltransferases in the length and orientation of these loops. Molecular dynamics simulation data suggest that these loops are highly dynamic, and ACO binding could affect their dynamics. Given that several proteins may undergo acetylation in H. pylori and the fact that HP0935 is the only known protein acetyltransferase, the loop dynamics are likely to facilitate the acceptance of multiple substrates by HP0935. Structure-based mutational analysis showed that no general base is required for the enzymatic activity. However, a conserved catalytic water molecule at the active site is likely to serve the purpose. Furthermore, the general acid Y127 is essential for enzymatic activity.

PubMed: 40505863
DOI: 10.1016/j.jbc.2025.110356

実験手法

X-RAY DIFFRACTION (2.4 Å)