Attacked by Radicals

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Science  10 May 2013:
Vol. 340, Issue 6133, pp. 662
DOI: 10.1126/science.340.6133.662-c

Some bonds are easy to break, and enzymes can handle these via general acid-base catalysis; other bonds are tougher nuts to crack, hence enzymes call upon more potent chemical weaponry, such as unpaired electrons. Phosphonate metabolism protein PhnJ is a member of the family of radical S-adenosyl-L-methionine (AdoMet) enzymes and breaks the C-P bond in methyl phosphonate. Kamat et al. show that the redox active iron-sulfur cluster in PhnJ converts AdoMet to the Ado-CH2· radical. They use isotopic labeling and mass spectrometry to establish that this radical pulls off the pro-R hydrogen from a nearby glycine residue to create a glycyl radical, which turns around and pulls off the hydrogen from a nearby cysteine to create a thiyl radical. It is this third radical that attacks the methyl phosphonate substrate, breaking the C-P bond by homolysis to form a thiophosphate intermediate and freeing the methyl moiety to grab the pro-S hydrogen (from the same glycine) as it exits as methane. The thiophosphate collapses intramolecularly to a cyclic phosphate, regenerating the sulfhydryl side chain, which can then go on to catalyze addi tional rounds of C-P cleavage in concert with the glycyl radical.

Nature 497, 132 (2013).

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