EC Number   |
General Information |
Reference |
|---|
   2.1.1.226 | evolution |
TlyA orthologues occur in diverse bacteria and fall into two distinct groups. One group, termed TlyAI, has shorter N- and C-termini and methylates only C1920. The second group, TlyAII, includes the mycobacterial enzyme, and these longer orthologues methylate at both C1409 (c.f. EC 2.1.1.227), and C1920 |
-, 720503 |
| 2.1.1.226 | malfunction |
deletion of the cj0588 gene in Campylobacter jejuni or substitution with alanine of K80, D162, or K188 in the catalytic center of the enzyme cause complete loss of 2'-O-methylation activity. Campylobacter jejuni strains expressing catalytically inactive versions of Cj0588 have the same phenotype as cj0588-null mutants, and show altered tolerance to capreomycin due to perturbed ribosomal subunit association, reduced motility and impaired ability to form biofilms. These functions are reestablished when methyltransferase activity is restored |
-, 756771 |
| 2.1.1.226 | malfunction |
disruption of the tlyA ORF can confer capreomycin resistance |
710879 |
| 2.1.1.226 | malfunction |
inactivation of TlyA and loss of its activity confer resistance to capreomycin and viomycin |
-, 720503 |
| 2.1.1.226 | malfunction |
loss-of-function mutations in rRNA methylase TlyA or point mutations in 16S rRNA, in particular the A1408G mutation. Both of these alterations result in resistance by reducing drug binding to the ribosome. Alterations of tlyA gene expression affect both antibiotic drug susceptibility and fitness cost of drug resistance. In particular, the common resistance mutation A1408G is accompanied by a physiological change that involves increased expression of the tlyA gene. This gene encodes an enzyme that methylates neighboring 16S rRNA position C1409, and as a result of increased TlyA expression the fitness cost of the A1408G mutation is significantly reduced |
-, 758323 |
| 2.1.1.226 | malfunction |
the bifunctional enzyme modifies nucleotide C1409 in helix 44 of 16S rRNA and nucleotide C1920 in helix 69 of 23S rRNA. Loss of these rRNA methylations confers resistance to capreomycin and viomycin |
713026 |
| 2.1.1.226 | metabolism |
antibiotic resistance mechanisms frequently confer a fitness cost, and these costs can be genetically ameliorated by intra- or extragenic second-site mutations, often without loss of resistance. Another mechanism by which the fitness cost of antibiotic resistance can be reduced is via a regulatory response where the deleterious effect of the resistance mechanism is lowered by a physiological alteration that buffers the mutational effect. In mycobacteria, resistance to the clinically used tuberactinomycin antibiotic capreomycin involves loss-of-function mutations in rRNA methylase TlyA or point mutations in 16S rRNA, in particular the A1408G mutation. Both of these alterations result in resistance by reducing drug binding to the ribosome. In mycobacteria, this nonmutational mechanism (i.e. gene regulatory) can restore fitness to genetically resistant bacteria. Incubation with capreomycin during bacterial growth resulted in a reduced post-transcriptional modification of rRNA at TlyA-dependent sites (1409 in 16S and 1920 in 23S), cf. EC 2.1.1.226 |
-, 758323 |
| 2.1.1.226 | more |
mechanism of Cj0588 action, overview. Homology modelling of the tertiary structure of the Cj0588 catalytic domain using Mycobacterium tuberculosis TlyA structure (PDB ID 5EOV) as a template. The HhaI methyltransferase structure (PDB ID 2HMY) is used to superimpose the AdoMet cofactor. Three-dimensional modeling of the catalytic domain of Cj0588 reveals a structure typical for 2'-O-methyltransferases with a seven-stranded beta-sheet between five alpha-helix layers and four residues K80, D162, K188 and E245 that comprise the catalytic center |
-, 756771 |
| 2.1.1.226 | more |
the cyclic peptide antibiotics capreomycin and viomycin bind on the ribosomal S70 subunit interface close to nucleotides C1409 in 16S rRNA and C1920 in 23S rRNA |
-, 720503 |
| 2.1.1.226 | more |
the S4-type RNA recognition domain (residues 5-64), S-adenosyl-methionine binding domain (residues 84-153), SAM-interacting residues (residues 90-94), and four catalytic residues (K69-D154-K182-E238) are conserved in 2'-O-methyltrasferases TlyA |
-, 735991 |
