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S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
S-adenosyl-L-methionine + cytidine1409 in 30S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 30S rRNA
additional information
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S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
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S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
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S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
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S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
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the bifunctional enzyme modifies nucleotide C1409 in helix 44 of 16S rRNA and nucleotide C1920 in helix 69 of 23S rRNA
the exact position of the methyl group in the wild-type rRNAs is verified by MALDI quadrupole-TOF tandem MS analysis
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S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
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S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
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S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
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S-adenosyl-L-methionine + cytidine1409 in 30S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 30S rRNA
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S-adenosyl-L-methionine + cytidine1409 in 30S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 30S rRNA
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additional information
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the 2'-O-methyltransferase TlyA from Mycobacterium tuberculosis methylates both nucleotide C1409 of 16S rRNA and C1920 of 23S rRNA, EC 2.1.1.226
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additional information
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the recombinant enzyme poorly modifies the nucleotide C1409 in vitro in all Escherichia coli ribosomal substrates evaluated: 16S rRNA, 30S ribosomal subunits, and 70S ribosomes
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additional information
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the bifunctional enzyme exhibits the activities of EC 2.1.1.226 and EC 2.1.1.227
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additional information
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the bifunctional enzyme exhibits the activities of EC 2.1.1.226 and EC 2.1.1.227
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additional information
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the 2'-O-methyltransferase TlyA from Mycobacterium tuberculosis methylates both nucleotide C1409 of 16S rRNA and C1920 of 23S rRNA, EC 2.1.1.226
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additional information
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the recombinant enzyme poorly modifies the nucleotide C1409 in vitro in all Escherichia coli ribosomal substrates evaluated: 16S rRNA, 30S ribosomal subunits, and 70S ribosomes
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additional information
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the TlyAII modifies C1409 in Escherichia coli 30S subunits, and activity at this site on 16S rRNA and 70S ribosomes is negligible
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additional information
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the TlyAII modifies C1409 in Escherichia coli 30S subunits, and activity at this site on 16S rRNA and 70S ribosomes is negligible
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S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
additional information
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S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
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S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
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S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
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S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
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S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
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S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
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additional information
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the 2'-O-methyltransferase TlyA from Mycobacterium tuberculosis methylates both nucleotide C1409 of 16S rRNA and C1920 of 23S rRNA, EC 2.1.1.226
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additional information
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the 2'-O-methyltransferase TlyA from Mycobacterium tuberculosis methylates both nucleotide C1409 of 16S rRNA and C1920 of 23S rRNA, EC 2.1.1.226
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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 results 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
evolution
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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 and C1920 (c.f. EC 2.1.1.226)
evolution
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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 and C1920 (c.f. EC 2.1.1.226)
evolution
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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 and C1920 (c.f. EC 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 and C1920 (c.f. EC 2.1.1.226)
evolution
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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 and C1920 (c.f. EC 2.1.1.226)
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evolution
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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 and C1920 (c.f. EC 2.1.1.226)
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malfunction
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disruption of the tlyA ORF can confer capreomycin resistance
malfunction
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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
malfunction
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inactivation of TlyA and loss of its activity confer resistance to capreomycin and viomycin
malfunction
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inactivation of TlyA and loss of its activity confer resistance to capreomycin and viomycin
malfunction
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inactivation of TlyA and loss of its activity confer resistance to capreomycin and viomycin
malfunction
inactivation of TlyA and loss of its activity confer resistance to capreomycin and viomycin
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
malfunction
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inactivation of TlyA and loss of its activity confer resistance to capreomycin and viomycin
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malfunction
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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
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malfunction
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inactivation of TlyA and loss of its activity confer resistance to capreomycin and viomycin
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physiological function
bacterial 2'-O-methyltransferase TlyA methylates either both nucleotide C1409 of 16S rRNA and C1920 of 23S rRNA. Both ribosomal methylations increase bacterial susceptibility to ribosome targeting antibiotics capreomycin and viomycin. The enzyme also function as a hemolysin, but increased bacterial hemolytic function is not likely a consequence of TlyA-mediated methylations of the ribosome
physiological function
TlyA methylase modifies the rRNA position 1409, reducing the cost of the A1408G mutation while concomitantly also reducing the antibiotic resistance level, e.g. against capreomycin and viomycin. In response to capreomycin, cells downregulate TlyA-mediated methylation of 16S and 23S rRNA resulting in decreased drug susceptibility. Increased TlyA expression reduces resistance in the A1408G mutant and concomitantly increases fitness
physiological function
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TlyA methylase modifies the rRNA position 1409, reducing the cost of the A1408G mutation while concomitantly also reducing the antibiotic resistance level, e.g. against capreomycin and viomycin. In response to capreomycin, cells downregulate TlyA-mediated methylation of 16S and 23S rRNA resulting in decreased drug susceptibility. Increased TlyA expression reduces resistance in the A1408G mutant and concomitantly increases fitness
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physiological function
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bacterial 2'-O-methyltransferase TlyA methylates either both nucleotide C1409 of 16S rRNA and C1920 of 23S rRNA. Both ribosomal methylations increase bacterial susceptibility to ribosome targeting antibiotics capreomycin and viomycin. The enzyme also function as a hemolysin, but increased bacterial hemolytic function is not likely a consequence of TlyA-mediated methylations of the ribosome
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additional information
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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
additional information
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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
additional information
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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
additional information
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
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expression of recombinant tlyA in Escherichia coli markedly increases susceptibility to the drugs capreomycin and viomycin
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gene tlyA, DNA and amino acid sequence determination, analysis and comparison, expression in Escherichia coli strain DH1
gene tlyA, recombinant expression of C-terminally His-tagged enzyme in Escherichia coli
gene tlyA, DNA and amino acid sequence determination, analysis and comparison, expression in Escherichia coli strain DH1
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gene tlyA, DNA and amino acid sequence determination, analysis and comparison, expression in Escherichia coli strain DH1
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gene tlyA, DNA and amino acid sequence determination, analysis and comparison, expression in Escherichia coli strain DH1
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gene tlyA, DNA and amino acid sequence determination, analysis and comparison, expression in Escherichia coli strain DH1
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Maus, C.E.; Plikaytis, B.B.; Shinnick, T.M.
Mutation of tlyA confers capreomycin resistance in Mycobacterium tuberculosis
Antimicrob. Agents Chemother.
49
571-577
2005
Mycobacterium tuberculosis
brenda
Johansen, S.K.; Maus, C.E.; Plikaytis, B.B.; Douthwaite, S.
Capreomycin binds across the ribosomal subunit interface using tlyA-encoded 2'-O-methylations in 16S and 23S rRNAs
Mol. Cell
23
173-182
2006
Mycobacterium tuberculosis
brenda
Monshupanee, T.; Johansen, S.K.; Dahlberg, A.E.; Douthwaite, S.
Capreomycin susceptibility is increased by TlyA-directed 2-O-methylation on both ribosomal subunits
Mol. Microbiol.
85
1194-1203
2012
Geobacillus stearothermophilus, Mycobacterium tuberculosis, no activity in Escherichia coli, Streptomyces coelicolor, Mycolicibacterium smegmatis (A0QYR0), Mycobacterium tuberculosis H37Rv, Mycolicibacterium smegmatis mc(2)155 (A0QYR0)
brenda
Monshupanee, T.
Increased bacterial hemolytic activity is conferred by expression of TlyA methyltransferase but not by its 2'-O-methylation of the ribosome
Curr. Microbiol.
67
61-68
2013
Mycobacterium tuberculosis (P9WJ63), Mycobacterium tuberculosis H37Rv (P9WJ63)
brenda
Freihofer, P.; Akbergenov, R.; Teo, Y.; Juskeviciene, R.; Andersson, D.; Boettger, E.
Nonmutational compensation of the fitness cost of antibiotic resistance in mycobacteria by overexpression of tlyA rRNA methylase
RNA
22
1836-1843
2016
Mycobacterium tuberculosis (P9WJ63), Mycobacterium tuberculosis H37Rv (P9WJ63)
brenda