The name of this superfamily has been modified since the most recent official CATH+ release (v4_3_0). At the point of the last release, this superfamily was named:

Ribosomal RNA adenine dimethylase-like, domain 2

Functional Families

Overview of the Structural Clusters (SC) and Functional Families within this CATH Superfamily. Clusters with a representative structure are represented by a filled circle.

Superfamily: rRNA adenine dimethylase, C-terminal domain

This superfamily represents the C-terminal domain of a universally conserved rRNA adenine dimethylase, KsgA. The N-terminal domain belongs to superfamily Most KsgA-like enzymes share a two-domain architecture with the larger N-terminal domain consisting of a mixed alpha/beta structure and a smaller C-terminal alpha-helical domain. KsgA is an S-adenosyl-L-methionine (AdoMet)-dependent methyltransferase responsible for producing the most highly conserved rRNA post-transcriptional modification, the N6, N6-dimethylation of two adjacent adenosines, A1518 and A1519 of 16S rRNA.

This enzyme and the resulting modified adenosine bases can be found across several species, such as eubacteria, eukaryotes, and archaebacteria, and in eukaryotic organelles. Despite this high level of conservation, the enzyme is not absolutely essential in bacteria. It has been shown that loss of KsgA activity is the most common mode of resistance to the antibiotic kasugamycin in E. coli and other bacteria. The yeast orthologue of KsgA is Dim1, and is essential since it is involved in ribosome biogenesis. Other KsgA orthologues has been found in human mitochondria (h-mtTFB26), mammalian mitochondria (TFB1 /TFB1M), and yeast mitochondria (sc-mtTFB). ErmC' from Bacillus subtilis is also structurally similar to KsgA.

KsgA catalyses the transfer of a total of four methyl groups from S-adenosyl-l-methionine (S-AdoMet) to two adjacent adenosine bases in 16S rRNA. The KsgA enzymes are homologous to another family of RNA methyltransferases, the Erm enzymes, which methylate a single adenosine base in 23S rRNA. Despite the high degree of structural similarity between KsgA and ErmC', KsgA has unique features that distinguish it from the Erm MTases. While the Erm MTases mono- or dimethylate a single adenosine base in 23 S rRNA, KsgA dimethylates two adenosine bases in 16 S rRNA. KsgA is subject to a complex regulation that is absent from the Erm enzymes.

The C-terminal domain of KsgA (as well as of other homologous enzymes) consists of four alpha-helices and one 3(10)-helix and forms a cleft with the N-terminal domain. The C-terminal domain has fewer conserved residues than the N-terminal domain. Among the conserved residues, motif VI contains three adjacent hydrophobic residues are suggested to be involved in proper positioning of the target adenosine base; the surface of the C-terminal domain contains many positively charged residues, which are highly conserved. The C-terminal domain seems to be an RNA-recognition domain - it does not play a direct role in RNA binding, but it is thought to stabilise the larger N-terminal domain PMID:15136037. Other studies have suggested that due to the positively charged surface patch, the C-terminal domain may be involved in recognition and binding of the ribosomal rRNA substrate, and mediates substrate specificity PMID:19285505,PMID:10366505,PMID:23804760.

PFAM:PF00398, INTERPRO:IPR023165,PMID:15136037,PMID:19285505,PMID:23804760,PMID:11567089,PMID:19278652,PMID:10366505,PMID:20163168

GO Diversity

Unique GO annotations
31 Unique GO terms

EC Diversity

Unique EC annotations
2 Unique EC terms

Species Diversity

Unique species annotations
14509 Unique species

Sequence/Structure Diversity

Overview of the sequence / structure diversity of this superfamily compared to other superfamilies in CATH. Click on the chart to view the data in more detail.

Superfamily Summary

A general summary of information for this superfamily.
Domains: 43
Domain clusters (>95% seq id): 12
Domain clusters (>35% seq id): 9
Unique PDBs: 31
Structural Clusters (5A): 1
Structural Clusters (9A): 1
FunFam Clusters: 35
Unique EC: 2
Unique GO: 31
Unique Species: 14509