InterPro domain: IPR006225

This entry represents the RluC/RluD subfamily of pseudouridine synthases. RluC and RluD are homologous enzymes which each convert three specific uridine bases in Escherichia coli ribosomal 23S RNA to pseudouridine: bases uracil-955, U-2504, and U-2580 in the case of RluC and uracil-1911, U-1915, and U-1917 in the case of RluD [ 1 ]. RluD also possesses a second function related to proper assembly of the 50S ribosomal subunit that is independent of Psi-synthesis [ 2 ]. Both RluC and RluD have an N-terminal S4 RNA binding domain. Despite the conserved topology shared by RluC and RluD, the surface shape and charge distribution are very different.

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 [ 3 , 4 ]:

• Pseudouridine synthase I, TruA.
• Pseudouridine synthase II, TruB, which contains and additional C-terminal PUA domain.
• Pseudouridine synthase RsuA. RluB, RluE and RluF are also part of this family.
• Pseudouridine synthase RluA. RluC and RluD belong to this family.
• 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.

1. Crystal structures of the catalytic domains of pseudouridine synthases RluC and RluD from Escherichia coli. Biochemistry 43, 4454-63
2. Crystal structure of the RluD pseudouridine synthase catalytic module, an enzyme that modifies 23S rRNA and is essential for normal cell growth of Escherichia coli. J. Mol. Biol. 335, 87-101
3. Role of cysteine residues in pseudouridine synthases of different families. Biochemistry 38, 13106-11
4. Enzymatic characterization and mutational studies of TruD--the fifth family of pseudouridine synthases. Arch. Biochem. Biophys. 489, 15-9