5MI4

BtGH84 mutant with covalent modification by MA3

5MI4 の概要

• エントリーDOI: 10.2210/pdb5mi4/pdb
• 分子名称: O-GlcNAcase BT_4395, ~{N}-(4-ethoxyquinazolin-2-yl)propanamide, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: hydrolase, activator
• 由来する生物種: Bacteroides thetaiotaomicron (strain ATCC 29148 / DSM 2079 / NCTC 10582 / E50 / VPI-5482)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 84197.15

構造登録者

Darby, J.F.,Davies, G.J.,Hubbard, R.E. (登録日: 2016-11-27, 公開日: 2017-11-01, 最終更新日: 2024-11-06)

主引用文献

Darby, J.F.,Atobe, M.,Firth, J.D.,Bond, P.,Davies, G.J.,O'Brien, P.,Hubbard, R.E.
Increase of enzyme activity through specific covalent modification with fragments.
Chem Sci, 8:7772-7779, 2017

PubMed Abstract: Modulation of enzyme activity is a powerful means of probing cellular function and can be exploited for diverse applications. Here, we explore a method of enzyme activation where covalent tethering of a small molecule to an enzyme can increase catalytic activity (/) up to 35-fold. Using a bacterial glycoside hydrolase, BtGH84, we demonstrate how small molecule "fragments", identified as activators in free solution, can be covalently tethered to the protein using Michael-addition chemistry. We show how tethering generates a constitutively-activated enzyme-fragment conjugate, which displays both improved catalytic efficiency and increased susceptibility to certain inhibitor classes. Structure guided modifications of the tethered fragment demonstrate how specific interactions between the fragment and the enzyme influence the extent of activation. This work suggests that a similar approach may be used to modulate the activity of enzymes such as to improve catalytic efficiency or increase inhibitor susceptibility.

PubMed: 29163914
DOI: 10.1039/c7sc01966a

実験手法

X-RAY DIFFRACTION (1.8 Å)