6533b839fe1ef96bd12a5c62
RESEARCH PRODUCT
Structure and Function of CutC Choline Lyase from Human Microbiota Bacterium Klebsiella pneumoniae.
Marina Makrecka-kukaMaija DambrovaJanis KukaKaspars TarsG. KalninsEdgars LiepinshSolveiga Grinbergasubject
Models MolecularKlebsiella pneumoniaeMetaboliteTrimethylamineLyasesmacromolecular substancesBiologydigestive systemBiochemistryMicrobiologyCholinechemistry.chemical_compoundBacterial ProteinsCatalytic DomainCholineChymotrypsinHumansMolecular Biologychemistry.chemical_classificationChymotrypsinMicrobiotaCell Biologybiology.organism_classificationLyaseEnzyme structureProtein Structure TertiaryKlebsiella pneumoniaeEnzymechemistryBiochemistrySpectrometry Mass Matrix-Assisted Laser Desorption-IonizationProtein Structure and Foldingbiology.proteinChromatography GelElectrophoresis Polyacrylamide GelProtein Multimerizationdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-08-01 | The Journal of biological chemistry |