InterPro: IPR001406 Pseudouridine synthase I, TruA

Pseudouridine synthases catalyse the isomerisation of uridine to pseudouridine (Psi) in a variety of RNA molecules, and may function as RNA chaperones. Pseudouridine is the most abundant modified nucleotide found in all cellular RNAs. There are four distinct families of pseudouridine synthases that share no global sequence similarity, but which do share the same fold of their catalytic domain(s) and uracil-binding site and are descended from a common molecular ancestor. The catalytic domain consists of two subdomains, each of which has an alpha+beta structure that has some similarity to the ferredoxin-like fold (note: some pseudouridine synthases contain additional domains). The active site is the most conserved structural region of the superfamily and is located between the two homologous domains. These families are [1]:

• Pseudouridine synthase I, TruA.
• Pseudouridine synthase II, TruB, which contains and additional C-terminal PUA domain.
• Pseudouridine synthase RsuA (ribosomal small subunit) and RluC/RluD (ribosomal large subunits), both of which contain an additional N-terminal alpha-L RNA-binding motif.
• Pseudouridine synthase TruD, which has a natural circular permutation in the catalytic domain, as well as an insertion of a family-specific alpha+beta subdomain.

This entry represents pseudouridine synthase I (TruA). TruA from Escherichia coli modifies positions uracil-38, U-39 and/or U-40 in tRNA [2, 3]. TruA contains one atom of zinc essential for its native conformation and tRNA recognition and has a strictly conserved aspartic acid that is likely to be involved in catalysis [4]. These enzymes are dimeric proteins that contain two positively charged, RNA-binding clefts along their surface. Each cleft contains a highly conserved aspartic acid located at its centre. The structural domains have a topological similarity to those of other RNA-binding proteins, though the mode of interaction with tRNA appears to be unique.