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Adenosyltransferase tailors and delivers coenzyme B12

Abstract

The reactivity and relative rarity of most cofactors pose challenges for their delivery to target enzymes. Using kinetic analyses, we demonstrate that adenosyltransferase, which catalyzes the final step in the assimilation of coenzyme B12, directly transfers the cofactor to methylmalonyl coenzyme A mutase. The strategy of using the final enzyme in an assimilation pathway for tailoring a cofactor and delivering it to a dependent enzyme may be general for cofactor trafficking.

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Figure 1: Direct transfer of AdoCbl between ATR and MCM.
Figure 2: Comparison between alternative mechanisms for AdoCbl transfer.
Figure 3: Role of histidine ligand in interprotein transfer of AdoCbl.

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Acknowledgements

This work was supported in part by a grant from the US National Institutes of Health (DK45776).

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Contributions

D.P. designed and performed the kinetic experiments, analyzed the data and helped write the paper. T.L. made the H596A and H596N mutants of MCM. B.A.P. and D.P.B. helped with the kinetic simulations, and R.B. helped design the experiments, analyze the data and write the paper.

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Correspondence to Ruma Banerjee.

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Supplementary Figures 1–6, Supplementary Tables 1–3 and Supplementary Methods (PDF 1162 kb)

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Padovani, D., Labunska, T., Palfey, B. et al. Adenosyltransferase tailors and delivers coenzyme B12. Nat Chem Biol 4, 194–196 (2008). https://doi.org/10.1038/nchembio.67

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