5NON

Structure of truncated Norcoclaurine Synthase from Thalictrum flavum with product mimic

5NON の概要

• エントリーDOI: 10.2210/pdb5non/pdb
• 関連するPDBエントリー: 5N8Q
• 分子名称: S-norcoclaurine synthase, 4-[2-[2-(4-methoxyphenyl)ethylamino]ethyl]benzene-1,2-diol (3 entities in total)
• 機能のキーワード: pictet spengler condensation, dopamine, lyase
• 由来する生物種: Thalictrum flavum subsp. glaucum (Yellow meadow rue)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 55576.25

構造登録者

Sula, A.,Lichman, B.R.,Pesnot, T.,Ward, J.M.,Hailes, H.C.,Keep, N.H. (登録日: 2017-04-12, 公開日: 2017-09-27, 最終更新日: 2024-05-08)

主引用文献

Lichman, B.R.,Sula, A.,Pesnot, T.,Hailes, H.C.,Ward, J.M.,Keep, N.H.
Structural Evidence for the Dopamine-First Mechanism of Norcoclaurine Synthase.
Biochemistry, 56:5274-5277, 2017

PubMed Abstract: Norcoclaurine synthase (NCS) is a Pictet-Spenglerase that catalyzes the first key step in plant benzylisoquinoline alkaloid metabolism, a compound family that includes bioactive natural products such as morphine. The enzyme has also shown great potential as a biocatalyst for the formation of chiral isoquinolines. Here we present new high-resolution X-ray crystallography data describing Thalictrum flavum NCS bound to a mechanism-inspired ligand. The structure supports two key features of the NCS "dopamine-first" mechanism: the binding of dopamine catechol to Lys-122 and the position of the carbonyl substrate binding site at the active site entrance. The catalytically vital residue Glu-110 occupies a previously unobserved ligand-bound conformation that may be catalytically significant. The potential roles of inhibitory binding and alternative amino acid conformations in the mechanism have also been revealed. This work significantly advances our understanding of the NCS mechanism and will aid future efforts to engineer the substrate scope and catalytic properties of this useful biocatalyst.

PubMed: 28915025
DOI: 10.1021/acs.biochem.7b00769

実験手法

X-RAY DIFFRACTION (1.85 Å)