InterPro domain: IPR034556

This entry respresents S-adenosyl-L-methionine-dependent tRNA 4-demethylwyosine synthase Tyw1 from eukaryotes and archaea. They are involved in the pathway wybutosine-tRNA(Phe) biosynthesis. It binds one [4Fe-4S] cluster and one [2Fe-2S] cluster. The [4Fe-4S] cluster is coordinated with three cysteines and an exchangeable S-adenosyl-L-methionine [ 1 , 2 ]. The two carbon source required for this reaction has been identified as pyruvate. The exact role of the SAM molecule has yet to be determined. There appear to be two distinct sets of proteins with different multi-domain architectures, however they are sufficiently similar in the Radical SAM portion that they remain a single cluster [ 3 ].

Wybutosine is a hyper modified guanosine with a tricyclic base found at the 3'-position adjacent to the anticodon of eukaryotic phenylalanine tRNA. It is important for translational reading-frame maintenance [ 4 ].

1. Structure of an archaeal TYW1, the enzyme catalyzing the second step of wye-base biosynthesis. Acta Crystallogr. D Biol. Crystallogr. 63, 1059-68
2. Structural characterization and comparative phylogenetic analysis of Escherichia coli HemK, a protein (N5)-glutamine methyltransferase. J. Mol. Biol. 340, 695-706
3. Pyruvate is the source of the two carbons that are required for formation of the imidazoline ring of 4-demethylwyosine. Biochemistry 50, 10573-5
4. Biosynthesis of wybutosine, a hyper-modified nucleoside in eukaryotic phenylalanine tRNA. EMBO J. 25, 2142-54