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  Carnitine metabolism in the human gut: characterization of the two-component carnitine monooxygenase CntAB fromAcinetobacter baumannii

Massmig, M., Reijerse, E. J., Krausze, J., Laurich, C., Lubitz, W., Jahn, D., et al. (2020). Carnitine metabolism in the human gut: characterization of the two-component carnitine monooxygenase CntAB fromAcinetobacter baumannii. The Journal of Biological Chemistry, 295(37), 13065-13078. doi:10.1074/jbc.RA120.014266.

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 Creators:
Massmig, Marco, Author
Reijerse, Eduard J.1, Author              
Krausze, Joern, Author
Laurich, Christoph1, Author              
Lubitz, Wolfgang2, Author              
Jahn, Dieter, Author
Moser, Juergen, Author
Affiliations:
1Research Department DeBeer, Max Planck Institute for Chemical Energy Conversion, Max Planck Society, ou_3023871              
2External Organizations, ou_persistent22              

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 Abstract: Bacterial formation of trimethylamine (TMA) from carnitine in the gut microbiome has been linked to cardiovascular disease. During this process, the two-component carnitine monooxygenase (CntAB) catalyzes the oxygen-dependent cleavage of carnitine to TMA and malic semialdehyde. Individual redox states of the reductase CntB and the catalytic component CntA were investigated based on mutagenesis and electron paramagnetic resonance (EPR) spectroscopic approaches. Protein ligands of the flavin mononucleotide (FMN) and the plant-type [2Fe-2S] cluster of CntB and also of the Rieske-type [2Fe-2S] cluster and the mononuclear [Fe] center of CntA were identified. EPR spectroscopy of variant CntA proteins suggested a hierarchical metallocenter maturation, Rieske [2Fe-2S] followed by the mononuclear [Fe] center. NADH-dependent electron transferviathe redox components of CntB and within the trimeric CntA complex for the activation of molecular oxygen was investigated. EPR experiments indicated that the two electrons from NADH were allocated to the plant-type [2Fe-2S] cluster and to FMN in the form of a flavin semiquinone radical. Single-turnover experiments of this reduced CntB species indicated the translocation of the first electron onto the [Fe] center and the second electron onto the Rieske-type [2Fe-2S] cluster of CntA to finally allow for oxygen activation as a basis for carnitine cleavage. EPR spectroscopic investigation of CntA variants indicated an unusual intermolecular electron transfer between the subunits of the CntA trimerviathe "bridging" residue Glu-205. On the basis of these data, a redox catalytic cycle for carnitine monooxygenase was proposed.

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Language(s): eng - English
 Dates: 2020
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000572412900016
DOI: 10.1074/jbc.RA120.014266
 Degree: -

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Title: The Journal of Biological Chemistry
  Alternative Title : JBC
Source Genre: Journal
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Publ. Info: Baltimore, etc. : American Society for Biochemistry and Molecular Biology [etc.]
Pages: - Volume / Issue: 295 (37) Sequence Number: - Start / End Page: 13065 - 13078 Identifier: ISSN: 0021-9258
n.a.: /journals/resource/954925410826_1