5KD0

Crystal structure of the aromatic prenyltransferase AtaPT(E91A) mutant from Aspergillus terreus A8-4 in complex with geranyl S-thiolodiphosphate and (+)-butyrolactone II

5KD0 の概要

• エントリーDOI: 10.2210/pdb5kd0/pdb
• 関連するPDBエントリー: 5KCG 5KCL 5KCQ 5KCY 5KD6 5KDA
• 分子名称: aromatic prenyltransferase, methyl (2~{R})-3-(4-hydroxyphenyl)-2-[(4-hydroxyphenyl)methyl]-4-oxidanyl-5-oxidanylidene-furan-2-carboxylate, GERANYL S-THIOLODIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: substrate promiscuity, abba fold, transferase
• 由来する生物種: Aspergillus terreus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 94037.52

構造登録者

Sun, F.,Gao, B. (登録日: 2016-06-07, 公開日: 2016-12-21, 最終更新日: 2023-11-08)

主引用文献

Chen, R.,Gao, B.,Liu, X.,Ruan, F.,Zhang, Y.,Lou, J.,Feng, K.,Wunsch, C.,Li, S.M.,Dai, J.,Sun, F.
Molecular insights into the enzyme promiscuity of an aromatic prenyltransferase.
Nat. Chem. Biol., 13:226-234, 2017

PubMed Abstract: Aromatic prenyltransferases (aPTases) transfer prenyl moieties from isoprenoid donors to various aromatic acceptors, some of which have the rare property of extreme enzymatic promiscuity toward both a variety of prenyl donors and a large diversity of acceptors. In this study, we discovered a new aPTase, AtaPT, from Aspergillus terreus that exhibits unprecedented promiscuity toward diverse aromatic acceptors and prenyl donors and also yields products with a range of prenylation patterns. Systematic crystallographic studies revealed various discrete conformations for ligand binding with donor-dependent acceptor specificity and multiple binding sites within a spacious hydrophobic substrate-binding pocket. Further structure-guided mutagenesis of active sites at the substrate-binding pocket is responsible for altering the specificity and promiscuity toward substrates and the diversity of product prenylations. Our study reveals the molecular mechanism underlying the promiscuity of AtaPT and suggests an efficient protein engineering strategy to generate new prenylated derivatives in drug discovery applications.

PubMed: 27992881
DOI: 10.1038/nchembio.2263

実験手法

X-RAY DIFFRACTION (2.82 Å)