6ND3

wild-type choline TMA lyase in complex with betaine aldehyde

6ND3 の概要

• エントリーDOI: 10.2210/pdb6nd3/pdb
• 分子名称: Choline trimethylamine-lyase, BETAINE ALDEHYDE (3 entities in total)
• 機能のキーワード: radical, lyase, barrel
• 由来する生物種: Desulfovibrio alaskensis (strain G20) (Desulfovibrio desulfuricans (strain G20))
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 760840.93

構造登録者

Funk, M.A.,Drennan, C.L. (登録日: 2018-12-13, 公開日: 2019-01-16, 最終更新日: 2024-11-20)

主引用文献

Orman, M.,Bodea, S.,Funk, M.A.,Campo, A.M.,Bollenbach, M.,Drennan, C.L.,Balskus, E.P.
Structure-Guided Identification of a Small Molecule That Inhibits Anaerobic Choline Metabolism by Human Gut Bacteria.
J.Am.Chem.Soc., 141:33-37, 2019

PubMed Abstract: The anaerobic gut microbial pathway that converts choline into trimethylamine (TMA) is broadly linked to human disease. Here, we describe the discovery that betaine aldehyde inhibits TMA production from choline by human gut bacterial isolates and a complex gut community. In vitro assays and a crystal structure suggest betaine aldehyde targets the gut microbial enzyme choline TMA-lyase (CutC). In our system, we do not observe activity for the previously reported CutC inhibitor 3,3-dimethylbutanol (DMB). The workflow we establish for identifying and characterizing betaine aldehyde provides a framework for developing additional inhibitors of gut microbial choline metabolism, including therapeutic candidates.

PubMed: 30557011
DOI: 10.1021/jacs.8b04883

実験手法

X-RAY DIFFRACTION (2.364 Å)