Crystal structure of the highly divergent pseudouridine synthase TruD reveals a circular permutation of a conserved fold

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Abstract
The pseudouridine (Ψ) synthases Pus7p and TruD define a family of RNA-modifying enzymes with no sequence similarity to previously characterized Ψ synthases. The 2.2 Å resolution structure of Escherichia coli TruD reveals a U-shaped molecule with a catalytic domain that superimposes closely on that of other Ψ synthases. A domain that appears to be unique to TruD/Pus7p family enzymes hinges over the catalytic domain, possibly serving to clasp the substrate RNAs. The active site comprises residues that are conserved in other Ψ synthases, although at least one comes from a structurally distinct part of the protein. Remarkably, the connectivity of the structural elements of the TruD catalytic domain is a circular permutation of that of its paralogs. Because the sequence of the permuted segment, a β-strand that bisects the catalytic domain, is conserved among orthologs from bacteria, archaea and eukarya, the permutation likely happened early in evolution.