Pathways & interactions
Pseudouridine synthase, RsuA/RluB/C/D/E/F (IPR006145)
Short name: PsdUridine_synth_RsuA/RluD
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 [PMID: 10529181]:
- 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 several different pseudouridine synthases from family 3, including: RsuA (acts on small ribosomal subunit), RluA, RluB, RluC, RluD, RluE and RluF (act on large ribosomal subunit).
RsuA from Escherichia coli catalyses formation of pseudouridine at position 516 in 16S rRNA during assembly of the 30S ribosomal subunit [PMID: 11953756, PMID: 16511038]. RsuA consists of an N-terminal domain connected by an extended linker to the central and C-terminal domains. Uracil and UMP bind in a cleft between the central and C-terminal domains near the catalytic residue Asp 102. The N-terminal domain shows structural similarity to the ribosomal protein S4. Despite only 15% amino acid identity, the other two domains are structurally similar to those of the tRNA-specific psi-synthase TruA, including the position of the catalytic Asp. Our results suggest that all four families of pseudouridine synthases share the same fold of their catalytic domain(s) and uracil-binding site.
RluB, RluC, RluD, RluE and RluF are homologous enzymes which each convert specific uridine bases in E. coli ribosomal 23S RNA to pseudouridine:
- RluB modifies uracil-2605.
- RluC modifies uracil-955, U-2504, and U-2580.
- RluD modifies uracil-1911, U-1915, and U-1917.
- RluE modifies uracil-3457.
- RluF modifies uracil-2604, and to a lesser extent U-2605.
RluD also possesses a second function related to proper assembly of the 50S ribosomal subunit that is independent of Psi-synthesis [PMID: 15078091, PMID: 14659742]. 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.