3awi | pdb_00003awi
Bifunctional tRNA modification enzyme MnmC from Escherichia coli
Structural highlights
Function[MNMC_ECOLI] Catalyzes the last two steps in the biosynthesis of 5-methylaminomethyl-2-thiouridine (mnm(5)s(2)U) at the wobble position (U34) in tRNA. Catalyzes the FAD-dependent demodification of cmnm(5)s(2)U34 to nm(5)s(2)U34, followed by the transfer of a methyl group from S-adenosyl-L-methionine to nm(5)s(2)U34, to form mnm(5)s(2)U34.[1] [2] Publication Abstract from PubMedPosttranscriptional modifications of bases within the tRNA anticodon significantly affect the decoding system. In bacteria and eukaryotes, uridines at the wobble position (U34) of some tRNAs are modified to 5-methyluridine derivatives (xm(5) U). These xm(5) U34-containing tRNAs read codons ending with A or G, while tRNAs with the unmodified U34 are able to read all four synonymous codons of a family box. In Escherichia coli, the bifunctional enzyme MnmC catalyzes the two consecutive reactions that convert 5-carboxymethylaminomethyl uridine (cmnm(5) U) to 5-methylaminomethyl uridine (mnm(5) U). The C-terminal domain of MnmC (MnmC1) is responsible for the FAD-dependent deacetylation of cmnm(5) U to 5-aminomethyl uridine (nm(5) U), while the N-terminal domain (MnmC2) catalyzes the subsequent S-adenosyl-L-methionine-dependent methylation of nm(5) U, leading to the final product, mnm(5) U34. Here, we determined the crystal structure of E. coli MnmC containing FAD, at 3.0 A resolution. The structure of the MnmC1 domain can be classified in the FAD-dependent glutathione reductase 2 (GR(2) ) structural family, including the glycine oxidase ThiO, while the MnmC2 domain adopts the canonical class I methyltransferase fold. A structural comparison with ThiO revealed the residues that may be involved in cmnm(5) U recognition, supporting previous mutational analyses. The catalytic sites of the two reactions are both surrounded by conserved basic residues for possible anticodon binding, and are located far away from each other, on opposite sides of the protein. These results suggest that, although the MnmC1 and MnmC2 domains are physically linked, they could catalyze the two consecutive reactions in a rather independent manner. Crystal structure of the bifunctional tRNA modification enzyme MnmC from Escherichia coli.,Kitamura A, Sengoku T, Nishimoto M, Yokoyama S, Bessho Y Protein Sci. 2011 May 13. doi: 10.1002/pro.659. PMID:21574198[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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