Methylase

Radical SAM methyltransferases

Based on different protein structures and mechanisms of catalysis, there are 3 different types of radical SAM (RS) methylases: Class A, B, and C. Class A RS methylases are the best characterized of the 4 enzymes and are related to both RlmN and Cfr. RlmN is ubiquitous in bacteria which enhances translational fidelity and RlmN catalyzes methylation of C2 of adenosine 2503 (A2503) in 23 S rRNA and C2 of adenosine (A37). Cfr, on the other hand, catalyzes methylation of C8 of A2503 as well and it also catalyzes C2 methylation. Class B is currently the largest class of radical SAM methylases which can methylate both sp2-hybridized and sp3-hybridized carbon atoms in different sets of substrates unlike Class A which only catalyzes sp2-hybridized carbon atoms. The main difference that distinguishes Class B from others is the additional N-terminal cobalamin-binding domain that binds to the RS domain. Class C methylase has homologous sequence with the RS enzyme, coproporphyrinogen III oxidase (HemN), which also catalyzes the methylation of sp2-hybridized carbon centers yet it lacks the 2 cysteines required for methylation in mechanism of Class A.