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Biological Chemistry

Methyl Handoff Between B Vitamins

Crystallographers visualize the dramatic protein conformational change required to transfer methyl from folate to vitamin B-12

by Amanda Yarnell
March 19, 2012 | A version of this story appeared in Volume 90, Issue 12

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Credit: Nature
Crystallography captured snapshots of vitamin B-12 (gray, green, and gold; cobalt is shown as a ball) on the move toward its B-9 methyl donor (gold at bottom left.)
Crystallography captured snapshots of vitamin B-12 (gray, green, and gold; cobalt is shown as a ball) on the move toward its B-9 methyl donor (red).
Credit: Nature
Crystallography captured snapshots of vitamin B-12 (gray, green, and gold; cobalt is shown as a ball) on the move toward its B-9 methyl donor (gold at bottom left.)

A dramatic conformational change is required for a key methyl transfer between two B vitamins, a crystallography study has shown (Nature, DOI: 10.1038/nature10916). The transfer of a methyl group from folate, also known as vitamin B-9, to vitamin B-12 is a key step in the synthesis of the amino acid methionine in humans. It also underlies the process by which certain bacteria manage to subsist on carbon dioxide. In both cases, huge protein complexes facilitate the seemingly simple methyl transfer step. MIT crystallographer Catherine L. Drennan and coworkers now offer the first glimpse at a 220-kilodalton complex in its entirety. Their 2.38-Å X-ray structure shows that methyl transfer between B-9 and B-12 requires a sweeping conformational change within the protein complex, where the domain bearing B-12 must move more than 25 Å to interact with the B-9 methyl donor. The researchers even managed to use UV-visible absorption spectroscopy to watch this move take place within the protein complex crystals—the largest protein conformational change ever observed in the crystalline state, Drennan says. The work “helps explain why such an elaborate protein framework is required for such a simple, yet biologically essential reaction,” the researchers write.

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