5GI5

Crystal Structure of Drosophila melanogaster Dopamine N-Acetyltransferase Bound to CoA

5GI5 の概要

• エントリーDOI: 10.2210/pdb5gi5/pdb
• 関連するPDBエントリー: 5GI6 5GI7 5GI8 5GI9
• 分子名称: Dopamine N-acetyltransferase, IMIDAZOLE, COENZYME A, ... (4 entities in total)
• 機能のキーワード: dopamine n-acetyltransferase(dat), gcn5-related n-acetyltransferase(gnat), arylalkylamine n-acetyltransferase(aanat), order bi-bi sequential mechanism, transferase
• 由来する生物種: Drosophila melanogaster (Fruit fly)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 25278.67

構造登録者

Yang, Y.C.,Cheng, H.C.,Lyu, P.C. (登録日: 2016-06-22, 公開日: 2017-07-05, 最終更新日: 2024-03-20)

主引用文献

Wu, C.Y.,Hu, I.C.,Yang, Y.C.,Ding, W.C.,Lai, C.H.,Lee, Y.Z.,Liu, Y.C.,Cheng, H.C.,Lyu, P.C.
An essential role of acetyl coenzyme A in the catalytic cycle of insect arylalkylamine N-acetyltransferase.
Commun Biol, 3:441-441, 2020

PubMed Abstract: Acetyl coenzyme A (Ac-CoA)-dependent N-acetylation is performed by arylalkylamine N-acetyltransferase (AANAT) and is important in many biofunctions. AANAT catalyzes N-acetylation through an ordered sequential mechanism in which cofactor (Ac-CoA) binds first, with substrate binding afterward. No ternary structure containing AANAT, cofactor, and substrate was determined, meaning the details of substrate binding and product release remain unclear. Here, two ternary complexes of dopamine N-acetyltransferase (Dat) before and after N-acetylation were solved at 1.28 Å and 1.36 Å resolution, respectively. Combined with the structures of Dat in apo form and Ac-CoA bound form, we addressed each stage in the catalytic cycle. Isothermal titration calorimetry (ITC), crystallography, and nuclear magnetic resonance spectroscopy (NMR) were utilized to analyze the product release. Our data revealed that Ac-CoA regulates the conformational properties of Dat to form the catalytic site and substrate binding pocket, while the release of products is facilitated by the binding of new Ac-CoA.

PubMed: 32796911
DOI: 10.1038/s42003-020-01177-9

実験手法

X-RAY DIFFRACTION (1.45 Å)