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Author Notes:

Corresponding Author: Ruma Banerjee Tel.: Phone: 734-615-5238; E-mail:rbanerje@umich.edu

Z. L. designed, performed, analyzed the experiments, and wrote the manuscript.

V. C. and K. K. purified IcmF and ATR and conceived and performed some of the initial experiments.

K. K. performed the GTPase activity assay.

D. C. performed some of the isothermal titration calorimetry experiments.

U. T. T. and K. W. performed the EPR analyses.

R. B. helped conceive the experiments, analyzed the data, and co-wrote the manuscript.

All authors approved the final version of the manuscript.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

The authors declare that they have no conflicts of interest with the contents of this article.


Research Funding:

This work was supported in part by National Institutes of Health Grant DK45776.


  • adenosylcobalamin (AdoCbl)
  • ATP
  • GTPase
  • low molecular weight G-protein
  • metalloprotein

Cofactor Editing by the G-protein Metallochaperone Domain Regulates the Radical B 12 Enzyme IcmF


Journal Title:

Journal of Biological Chemistry


Volume 292, Number 10


, Pages 3977-3987

Type of Work:

Article | Final Publisher PDF


IcmF is a 5′-deoxyadenosylcobalamin (AdoCbl)-dependent enzyme that catalyzes the carbon skeleton rearrangement of isobutyryl-CoA to butyryl-CoA. It is a bifunctional protein resulting from the fusion of a G-protein chaperone with GTPase activity and the cofactor- and substrate-binding mutase domains with isomerase activity. IcmF is prone to inactivation during catalytic turnover, thus setting up its dependence on a cofactor repair system. Herein, we demonstrate that the GTPase activity of IcmF powers the ejection of the inactive cob(II)alamin cofactor and requires the presence of an acceptor protein, adenosyltransferase, for receiving it. Adenosyltransferase in turn converts cob(II)alamin to AdoCbl in the presence of ATP and a reductant. The repaired cofactor is then reloaded onto IcmF in a GTPase-gated step. The mechanistic details of cofactor loading and offloading from the AdoCbl-dependent IcmF are distinct from those of the better characterized and homologous methylmalonyl-CoA mutase/G-protein chaperone system.

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© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

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