Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2012) Nucleic Acids Res , doi:10.1093/nar/gkr931

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rADc Ribosomal RNA adenine dimethylases

SMART accession number:	SM00650
Description:
Interpro abstract (IPR020598):	This family of proteins include rRNA adenine dimethylases (e.g. KsgA) and the Erythromycin resistance methylases (Erm). The bacterial enzyme 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. This enzyme and the resulting modified adenosine bases appear to be conserved in all species of eubacteria, eukaryotes, and archaea, and in eukaryotic organelles. Bacterial resistance to the aminoglycoside antibiotic kasugamycin involves inactivation of KsgA and resulting loss of the dimethylations, with modest consequences to the overall fitness of the organism. In contrast, the yeast ortholog, Dim1, is essential. In Saccharomyces cerevisiae (Baker's yeast), and presumably in other eukaryotes, the enzyme performs a vital role in pre-rRNA processing in addition to its methylating activity. The best conserved region in these enzymes is located in the N-terminal section and corresponds to a region that is probably involved in S-adenosyl methionine (SAM) binding domain. The crystal structure of KsgA from Escherichia coli has been solved to a resolution of 2.1A. It bears a strong similarity to the crystal structure of ErmC' from Bacillus stearothermophilus and a lesser similarity to the yeast mitochondrial transcription factor, sc-mtTFB [(PUBMED:15136037)]. The Erm family of RNA methyltransferases, which methylate a single adenosine base in 23S rRNA confer resistance to the MLS-B group of antibiotics. Despite their sequence similarity, the two enzyme families have strikingly different levels of regulation that remain to be elucidated. Other orthologs, of this family include the yeast and Homo sapiens (Human) mitochondrial transcription factors (MTF1 and h-mtTFB respectively), which are nuclear encoded [(PUBMED:11567089)]. Human-mtTFB is able to stimulate transcription in vitro independently of its S-adenosylmethionine binding and rRNA methyltransferase activity [(PUBMED:12897151)]. This entry represents the N-terminal domain of rRNA adenine methylase transferases.
GO process:	rRNA modification (GO:0000154)
GO function:	rRNA methyltransferase activity (GO:0008649), rRNA (adenine-N6,N6-)-dimethyltransferase activity (GO:0000179)
Family alignment:	View or CHROMA formatCLUSTALW formatMSF formatFASTA formatPIR format

There are 2096 rADc domains in 2096 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Click on to expand nodes. To display all proteins with a rADc domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with rADc domain is also avaliable.

  Useful shortcuts: Expand all nodes or Collapse tree
  Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae, Takifugu rubripes

• Cellular role (predicted cellular role)

• Cellular role: translation
  Binding / catalysis: RNA-binding

• Literature (relevant references for this domain)

• Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

  • Yu L et al.
  • Solution structure of an rRNA methyltransferase (ErmAM) that confers macrolide-lincosamide-streptogramin antibiotic resistance.
  • Nat Struct Biol. 1997; 4: 483-9
  • Display abstract

  • The Erm family of methyltransferases is responsible for the development of resistance to the macrolide-lincosamide-streptogramin type B (MLS) antibiotics. These enzymes methylate an adenine of 23S ribosomal RNA that prevents the MLS antibiotics from binding to the ribosome and exhibiting their antibacterial activity. Here we describe the three-dimensional structure of an Erm family member, ErmAM, as determined by NMR spectroscopy. The catalytic domain of ErmAM is structurally similar to that found in other methyltransferases and consists of a seven-stranded beta-sheet flanked by alpha-helices and a small two-stranded beta-sheet. In contrast to the catalytic domain, the substrate binding domain is different from other methyltransferases and adopts a novel fold that consists of four alpha-helices.

• Metabolism (metabolic pathways involving proteins which contain this domain)

• Click the image to view the interactive version of the map in iPath

  % proteins involved KEGG pathway ID Description 14.29 map00350 Tyrosine metabolism 14.29 map00450 Selenoamino acid metabolism 14.29 map00380 Tryptophan metabolism 14.29 map00440 Aminophosphonate metabolism 14.29 map00626 Naphthalene and anthracene degradation 14.29 map00150 Androgen and estrogen metabolism 14.29 map00340 Histidine metabolism This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with rADc domain which could be assigned to a KEGG orthologous group, and not all proteins containing rADc domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

• Structure (3D structures containing this domain)

• 3D Structures of rADc domains in PDB

  PDB code	Main view	Title
  1qam		The structure of the rrna methyltransferase ermc': implications for the reaction mechanism
  1qan		The structure of the rrna methyltransferase ermc': implications for the reaction mechanism
  1qao		The structure of the rrna methyltransferase ermc': implications for the reaction mechanism
  1qaq		The structure of the rrna methyltransferase ermc': implications for the reaction mechanism
  1qyr		2.1 angstrom crystal structure of ksga: a universally conserved adenosine dimethyltransferase
  1yub		Solution structure of an rrna methyltransferase (ermam) that confers macrolide-lincosamide-streptogramin antibiotic resistance, nmr, minimized average structure
  1zq9		Crystal structure of human dimethyladenosine transferase
  2erc		Crystal structure of ermc' a rrna-methyl transferase
  2h1r		Crystal structure of a dimethyladenosine transferase from plasmodium falciparum
  3ftc		Crystal structure of a. aeolicus ksga at 1.72-angstrom resolution
  3ftd		Crystal structure of a. aeolicus ksga at 1.44-angstrom resolution
  3fte		Crystal structure of a. aeolicus ksga in complex with rna
  3ftf		Crystal structure of a. aeolicus ksga in complex with rna and sah
  3fut		Apo-form of t. thermophilus 16s rrna a1518 and a1519 methyltransferase (ksga) in space group p21212
  3fuu		T. thermophilus 16s rrna a1518 and a1519 methyltransferase (ksga) in complex with adenosine in space group p212121
  3fuv		Apo-form of t. thermophilus 16s rrna a1518 and a1519 methyltransferase (ksga) in space group p43212
  3fuw		T. thermophilus 16s rrna a1518 and a1519 methyltransferase (ksga) in complex with 5'-methylthioadenosine in space group p212121
  3fux		T. thermophilus 16s rrna a1518 and a1519 methyltransferase (ksga) in complex with 5'-methylthioadenosine in space group p212121
  3fyc		Crystal structure of dim1 from the thermophilic archeon, methanocaldococcus jannaschi
  3fyd		Crystal structure of dim1 from the thermophilic archeon, methanocaldococcus jannaschi

• Links (links to other resources describing this domain)

• PFAM	RrnaAD
  INTERPRO	IPR020598

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