7A20

Azobenzene-Based Inhibitors for Tryptophan Synthase

7A20 の概要

• エントリーDOI: 10.2210/pdb7a20/pdb
• 分子名称: Tryptophan synthase alpha chain,Tryptophan synthase beta chain, SODIUM ION, TRIS-HYDROXYMETHYL-METHYL-AMMONIUM, ... (4 entities in total)
• 機能のキーワード: antibiotics, enzymes, inhibitors, photopharmacology, photoswitches, antibiotic
• 由来する生物種: Salmonella typhimurium; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 306114.58

構造登録者

Rajendran, C.,Sterner, R. (登録日: 2020-08-14, 公開日: 2020-11-04, 最終更新日: 2024-05-15)

主引用文献

Simeth, N.A.,Kinateder, T.,Rajendran, C.,Nazet, J.,Merkl, R.,Sterner, R.,Konig, B.,Kneuttinger, A.C.
Towards Photochromic Azobenzene-Based Inhibitors for Tryptophan Synthase.
Chemistry, 27:2439-2451, 2021

PubMed Abstract: Light regulation of drug molecules has gained growing interest in biochemical and pharmacological research in recent years. In addition, a serious need for novel molecular targets of antibiotics has emerged presently. Herein, the development of a photocontrollable, azobenzene-based antibiotic precursor towards tryptophan synthase (TS), an essential metabolic multienzyme complex in bacteria, is presented. The compound exhibited moderately strong inhibition of TS in its E configuration and five times lower inhibition strength in its Z configuration. A combination of biochemical, crystallographic, and computational analyses was used to characterize the inhibition mode of this compound. Remarkably, binding of the inhibitor to a hitherto-unconsidered cavity results in an unproductive conformation of TS leading to noncompetitive inhibition of tryptophan production. In conclusion, we created a promising lead compound for combatting bacterial diseases, which targets an essential metabolic enzyme, and whose inhibition strength can be controlled with light.

PubMed: 33078454
DOI: 10.1002/chem.202004061

実験手法

X-RAY DIFFRACTION (2.5 Å)