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

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 hig...

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Vydáno v:The Journal of biological chemistry Ročník 290; číslo 35; s. 21732 - 21740
Hlavní autoři: Kalnins, Gints, Kuka, Janis, Grinberga, Solveiga, Makrecka-Kuka, Marina, Liepinsh, Edgars, Dambrova, Maija, Tars, Kaspars
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 28.08.2015
Témata:
Bacterial Proteins - chemistry
Bacterial Proteins - metabolism
Catalytic Domain
Choline - metabolism
Chromatography, Gel
Chymotrypsin - metabolism
Electrophoresis, Polyacrylamide Gel
Humans
Klebsiella pneumoniae - enzymology
Lyases - chemistry
Lyases - metabolism
Microbiota
Models, Molecular
Protein Multimerization
Protein Structure, Tertiary
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
choline
enzyme catalysis
radical
conformational change
enzyme structure
ISSN:1083-351X
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Popis
Shrnutí: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.
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ISSN:1083-351X
DOI:10.1074/jbc.M115.670471