SPASM and Twitch Domains in AdoMet Radical Enzyme Structures [Protein Structure and Folding]

December 4th, 2014 by Grell, T. A. J., Goldman, P. J., Drennan, C. L.

S-adenosylmethionine (AdoMet) radical enzymes use S-adenosylmethionine AdoMet and a [4Fe-4S] cluster to catalyze a diverse array of reactions. They adopt a partial TIM barrel fold with N- and C-terminal extensions that tailor the structure of the enzyme to its specific function. One extension, termed a SPASM domain, binds two auxiliary [4Fe-4S] clusters and is present within peptide-modifying enzymes. The first structure of a SPASM-containing enzyme, anaerobic sulfatase maturating enyzme, revealed unexpected similarities to two non-SPASM proteins, butirosin biosynthetic enzyme BtrN and molybdenum cofactor biosynthetic enzyme MoaA. The latter two enzymes bind one auxiliary cluster and exhibit a partial SPASM motif, coined a Twitch domain. Here we review the function, structure, and role of auxiliary cluster domains within the AdoMet radical enzyme superfamily.