6nd3
wild-type choline TMA lyase in complex with betaine aldehyde
Structural highlights
FunctionCUTC_OLEA2 Glycine radical enzyme that catalyzes the cleavage of a C-N bond in choline, producing trimethylamine (TMA) and acetaldehyde (PubMed:23151509, PubMed:24854437). Is involved in the anaerobic choline utilization pathway that allows D.alaskensis to grow on choline as a source of carbon and energy (PubMed:23151509). Is strictly specific for choline as substrate (PubMed:24854437).[1] [2] Publication Abstract from PubMedThe 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. Structure-Guided Identification of a Small Molecule That Inhibits Anaerobic Choline Metabolism by Human Gut Bacteria.,Orman M, Bodea S, Funk MA, Campo AM, Bollenbach M, Drennan CL, Balskus EP J Am Chem Soc. 2018 Dec 17. doi: 10.1021/jacs.8b04883. PMID:30557011[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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