Attacked by Radicals

Abstract

Biochemistry 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).