8J5V

Crystal structure of estZF172 as a novel biocatalyst for the efficient biosynthesis of a chiral intermediate of pregabalin

8J5V の概要

• エントリーDOI: 10.2210/pdb8j5v/pdb
• 分子名称: Carboxylesterase (2 entities in total)
• 機能のキーワード: esterase/lipase family viii, carboxylesterase, lyase
• 由来する生物種: Pseudomonas putida (Arthrobacter siderocapsulatus)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 44055.52

構造登録者

Chi, C.B.,Liang, Z.D.,Huo, B.Q.,Hu, C.X.,Sun, Q.Y. (登録日: 2023-04-24, 公開日: 2024-05-01, 最終更新日: 2025-12-10)

主引用文献

Liang, Z.,Ma, X.,Sun, Q.,Zhang, X.,Wang, G.,Chi, C.
Crystal Structure of EstZF172 Catalyzing Stereoselectively ( R )‐CNDE in Pregabalin Biosynthesis.
Acs Omega, 10:21693-21700, 2025

PubMed Abstract: Pregabalin has garnered extensive clinical application for the management of neuropathic pain and epilepsy owing to its high efficacy and broad drug concentration range. EstZF172 is a key enzyme in the biosynthesis of pregabalin, capable of stereoselectively catalyzing the production of ()-CCMA from the key intermediate -CNDE. The novel crystal structure of EstZF172 indicates that it contains a highly conserved Ser-Lys-Tyr catalytic triad and belongs to the family VIII carboxylesterases. Molecular docking demonstrates that the steric hindrance presented by residues I159 and F239 plays a crucial role in influencing the binding affinity of the chiral substrate ()-CNDE for the catalytic site. The study provides a structural basis and reference for the stereoselective catalysis of EstZF172 and engineering modification of the key enzyme in the synthesis of pregabalin.

PubMed: 40488026
DOI: 10.1021/acsomega.5c01054

実験手法

X-RAY DIFFRACTION (2.05 Å)