Radical S-adenosylmethionine (SAM) (RS) methylases perform methylation reactions at unactivated carbon and phosphorus atoms. RS enzymes typically abstract a hydrogen from their substrates, generating a substrate-centered radical; class B RS methylases catalyze methyl transfer from SAM to cobalamin and then to a substrate-centered carbon or phosphorus radical. Radle et al. now show that Mmp10, an RS enzyme implicated in the methylation of Arg-285 in methyl coenzyme M reductase, binds a methylcobalamin cofactor required for methyl transfer from SAM to a peptide substrate.
