6ND3

wild-type choline TMA lyase in complex with betaine aldehyde

Summary for 6ND3

• Entry DOI: 10.2210/pdb6nd3/pdb
• Descriptor: Choline trimethylamine-lyase, BETAINE ALDEHYDE (3 entities in total)
• Functional Keywords: radical, lyase, barrel
• Biological source: Desulfovibrio alaskensis (strain G20) (Desulfovibrio desulfuricans (strain G20))
• Total number of polymer chains: 8
• Total formula weight: 760840.93

Authors

Funk, M.A.,Drennan, C.L. (deposition date: 2018-12-13, release date: 2019-01-16, Last modification date: 2023-10-11)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.364 Å)