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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:The Journal of biological chemistry Jg. 290; H. 35; S. 21732 - 21740
Hauptverfasser: Kalnins, Gints, Kuka, Janis, Grinberga, Solveiga, Makrecka-Kuka, Marina, Liepinsh, Edgars, Dambrova, Maija, Tars, Kaspars
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 28.08.2015
Schlagworte:
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
Online-Zugang:Weitere Angaben
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1083-351X
DOI:10.1074/jbc.M115.670471