Dataset Information

Structure and Function of CutC Choline Lyase from Human Microbiota Bacterium Klebsiella pneumoniae.

ABSTRACT: CutC choline trimethylamine-lyase is an anaerobic bacterial glycyl radical enzyme (GRE) that cleaves choline to produce trimethylamine (TMA) and acetaldehyde. In humans, TMA is produced exclusively by the intestinal microbiota, and its metabolite, trimethylamine oxide, has been associated with a higher risk of cardiovascular diseases. Therefore, information about the three-dimensional structures of TMA-producing enzymes is important for microbiota-targeted drug discovery. We have cloned, expressed, and purified the CutC GRE and the activating enzyme CutD from Klebsiella pneumoniae, a representative of the human microbiota. We have determined the first crystal structures of both the choline-bound and choline-free forms of CutC and have discovered that binding of choline at the ligand-binding site triggers conformational changes in the enzyme structure, a feature that has not been observed for any other characterized GRE.

SUBMITTER: Kalnins G

PROVIDER: S-EPMC4571895 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Structure and Function of CutC Choline Lyase from Human Microbiota Bacterium Klebsiella pneumoniae.

Kalnins Gints G Kuka Janis J Grinberga Solveiga S Makrecka-Kuka Marina M Liepinsh Edgars E Dambrova Maija M Tars Kaspars K

The Journal of biological chemistry 20150717 35

CutC choline trimethylamine-lyase is an anaerobic bacterial glycyl radical enzyme (GRE) that cleaves choline to produce trimethylamine (TMA) and acetaldehyde. In humans, TMA is produced exclusively by the intestinal microbiota, and its metabolite, trimethylamine oxide, has been associated with a higher risk of cardiovascular diseases. Therefore, information about the three-dimensional structures of TMA-producing enzymes is important for microbiota-targeted drug discovery. We have cloned, express ...[more]

PMID: 26187464

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Dataset Information

Structure and Function of CutC Choline Lyase from Human Microbiota Bacterium Klebsiella pneumoniae.

Publications

Structure and Function of CutC Choline Lyase from Human Microbiota Bacterium Klebsiella pneumoniae.

Similar Datasets

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