Pathways & interactions
Pseudouridine synthase, catalytic domain superfamily (IPR020103)
Short name: PsdUridine_synth_cat_dom_sf
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.
TruA from Escherichia coli modifies positions U-38, U-39 and/or U-40 in tRNA [PMID: 10625422, PMID: 17466622]. 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 [PMID: 9585540]. 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.
TruB is responsible for the pseudouridine residue present in the T loops of virtually all tRNAs. TruB recognises the preformed 3-D structure of the T loop primarily through shape complementarity. It accesses its substrate uridyl residue by flipping out the nucleotide and disrupts the tertiary structure of tRNA [PMID: 11779468].
RsuA from E. coli catalyses formation of pseudouridine at position U-516 in 16S rRNA during assembly of the 30S ribosomal subunit [PMID: 11953756]. 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.
RluC and RluD are homologous enzymes which each convert three specific uridine bases in E. coli ribosomal 23S RNA to pseudouridine: bases U-955, U-2504, and U-2580 in the case of RluC and U-1911, U-1915, and U-1917 in the case of RluD [PMID: 15078091]. RluD also possesses a second function related to proper assembly of the 50S ribosomal subunit that is independent of Psi-synthesis [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.
TruD modifies uracil-13 in tRNA, and belongs to a recently identified and large family of pseudouridine synthases present in all kingdoms of life [PMID: 15135053]. TruD is an overall V-shaped molecule with an RNA-binding cleft formed between two domains: a catalytic domain and an insertion domain. The catalytic domain has a fold similar to that of the catalytic domains of previously characterised pseudouridine synthases, whereas the insertion domain displays a novel fold.
- SSF55120 (SSF55120)