5UGI

Crystal Structure of Ketosteroid Isomerase D38GF54A mutant from Pseudomonas Testosteroni (tKSI) bound to Equilenin

5UGI の概要

• エントリーDOI: 10.2210/pdb5ugi/pdb
• 分子名称: Steroid Delta-isomerase, EQUILENIN (3 entities in total)
• 機能のキーワード: enzyme, isomerase
• 由来する生物種: Comamonas testosteroni
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13544.30

構造登録者

Yabukarski, F.,Lamba, V.,Herschlag, D. (登録日: 2017-01-08, 公開日: 2017-11-15, 最終更新日: 2023-10-04)

主引用文献

Lamba, V.,Yabukarski, F.,Herschlag, D.
An Activator-Blocker Pair Provides a Controllable On-Off Switch for a Ketosteroid Isomerase Active Site Mutant.
J. Am. Chem. Soc., 139:11089-11095, 2017

PubMed Abstract: Control of enzyme activity is fundamental to biology and represents a long-term goal in bioengineering and precision therapeutics. While several powerful molecular strategies have been developed, limitations remain in their generalizability and dynamic range. We demonstrate a control mechanism via separate small molecules that turn on the enzyme (activator) and turn off the activation (blocker). We show that a pocket created near the active site base of the enzyme ketosteriod isomerase (KSI) allows efficient and saturable base rescue when the enzyme's natural general base is removed. Binding a small molecule with similar properties but lacking general-base capability in this pocket shuts off rescue. The ability of small molecules to directly participate in and directly block catalysis may afford a broad controllable dynamic range. This approach may be amenable to numerous enzymes and to engineering and screening approaches to identify activators and blockers with strong, specific binding for engineering and therapeutic applications.

PubMed: 28719738
DOI: 10.1021/jacs.7b03547

実験手法

X-RAY DIFFRACTION (1.8 Å)