6VUE

wild-type choline TMA lyase in complex with 1-methyl-1,2,3,6-tetrahydropyridin-3-ol

6VUE の概要

• エントリーDOI: 10.2210/pdb6vue/pdb
• 分子名称: Choline trimethylamine-lyase, SODIUM ION, (3S)-1-methyl-1,2,3,6-tetrahydropyridin-3-ol, ... (4 entities in total)
• 機能のキーワード: choline-tma lyase, microbiome choline cutc inhibitor, lyase, lyase-inhibitor complex, lyase/inhibitor
• 由来する生物種: Desulfovibrio alaskensis (strain G20)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 183444.55

構造登録者

Ortega, M.A.,Drennan, C.L. (登録日: 2020-02-15, 公開日: 2020-11-04, 最終更新日: 2023-10-11)

主引用文献

Bollenbach, M.,Ortega, M.,Orman, M.,Drennan, C.L.,Balskus, E.P.
Discovery of a Cyclic Choline Analog That Inhibits Anaerobic Choline Metabolism by Human Gut Bacteria.
Acs Med.Chem.Lett., 11:1980-1985, 2020

PubMed Abstract: The anaerobic conversion of choline to trimethylamine (TMA) by the human gut microbiota has been linked to multiple human diseases. The potential impact of this microbial metabolic activity on host health has inspired multiple efforts to identify small molecule inhibitors. Here, we use information about the structure and mechanism of the bacterial enzyme choline TMA-lyase (CutC) to develop a cyclic choline analog that inhibits the conversion of choline to TMA in bacterial whole cells and in a complex gut microbial community. biochemical assays and a crystal structure suggest that this analog is a competitive, mechanism-based inhibitor. This work demonstrates the utility of structure-based design to access inhibitors of radical enzymes from the human gut microbiota.

PubMed: 33062182
DOI: 10.1021/acsmedchemlett.0c00005

実験手法

X-RAY DIFFRACTION (2.28 Å)