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Information on EC 2.1.1.227 - 16S rRNA (cytidine1409-2'-O)-methyltransferase
for references in articles please use BRENDA:EC2.1.1.227
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EC Tree 2 Transferases
2.1 Transferring one-carbon groups
2.1.1 Methyltransferases
2.1.1.227 16S rRNA (cytidine1409-2'-O)-methyltransferase
IUBMB Comments
The bifunctional enzyme from Mycobacterium tuberculosis 2′-O-methylates cytidine1409 in helix 44 of 16S rRNA and cytidine1920 in helix 69 of 23S rRNA (cf. EC 2.1.1.226, 23S rRNA (cytidine1920-2′-O)-methyltransferase).
The enzyme appears in viruses and cellular organisms
Reaction Schemes
show+
=
+
+
cytidine1409 in 16S rRNA
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2'-O-methylcytidine1409 in 16S rRNA
Synonyms
2'-O-methyltransferase, More, rRNA methylase, rRNA methylase TlyA, TlyA, TlyAII, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
2'-O-methyltransferase
TlyA
TlyAII
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
S-adenosyl-L-methionine + cytidine1409 in 16S rRNA = S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
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SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:16S rRNA (cytidine1409-2'-O)-methyltransferase
The bifunctional enzyme from Mycobacterium tuberculosis 2'-O-methylates cytidine1409 in helix 44 of 16S rRNA and cytidine1920 in helix 69 of 23S rRNA (cf. EC 2.1.1.226, 23S rRNA (cytidine1920-2'-O)-methyltransferase).
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
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
S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
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Substrates: -
Products: -
Products: -
?
S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
-
Substrates: -
Products: -
Products: -
?
S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
-
Substrates: the bifunctional enzyme modifies nucleotide C1409 in helix 44 of 16S rRNA and nucleotide C1920 in helix 69 of 23S rRNA
Products: the exact position of the methyl group in the wild-type rRNAs is verified by MALDI quadrupole-TOF tandem MS analysis
Products: the exact position of the methyl group in the wild-type rRNAs is verified by MALDI quadrupole-TOF tandem MS analysis
?
S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
-
Substrates: -
Products: -
Products: -
?
S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
Substrates: -
Products: -
Products: -
?
S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
-
Substrates: -
Products: -
Products: -
?
S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
Substrates: -
Products: -
Products: -
?
S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
-
Substrates: -
Products: -
Products: -
?
S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
-
Substrates: -
Products: -
Products: -
?
S-adenosyl-L-methionine + cytidine1409 in 30S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 30S rRNA
Substrates: -
Products: -
Products: -
?
S-adenosyl-L-methionine + cytidine1409 in 30S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 30S rRNA
Substrates: -
Products: -
Products: -
?
additional information
?
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
Substrates: the bifunctional enzyme exhibits the activities of EC 2.1.1.226 and EC 2.1.1.227
Products: -
Products: -
?
additional information
?
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
Substrates: the bifunctional enzyme exhibits the activities of EC 2.1.1.226 and EC 2.1.1.227
Products: -
Products: -
?
additional information
?
-
Substrates: the TlyAII modifies C1409 in Escherichia coli 30S subunits, and activity at this site on 16S rRNA and 70S ribosomes is negligible
Products: -
Products: -
?
additional information
?
-
Substrates: the TlyAII modifies C1409 in Escherichia coli 30S subunits, and activity at this site on 16S rRNA and 70S ribosomes is negligible
Products: -
Products: -
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
-
Substrates: -
Products: -
Products: -
?
S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
-
Substrates: -
Products: -
Products: -
?
S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
Substrates: -
Products: -
Products: -
?
S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
-
Substrates: -
Products: -
Products: -
?
S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
Substrates: -
Products: -
Products: -
?
S-adenosyl-L-methionine + cytidine1409 in 16S rRNA
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1409 in 16S rRNA
-
Substrates: -
Products: -
Products: -
?
additional information
?
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
Substrates: 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
Products: -
Products: -
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
50
37
-
assay at with Mycobacterium smegmatis ribosomal substrates
37
assay at with Mycobacterium smegmatis ribosomal substrates
50
assay at with Thermus thermophilus ribosomal substrates
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
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
-
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)
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
malfunction
-
disruption of the tlyA ORF can confer capreomycin resistance
malfunction
-
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
-
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
-
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
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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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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
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
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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
-
when Mycobacterium smegmatis bifunctional TlyA-II catalyzing reaction of EC 2.1.1.226 and 2.1.1.227 is expressed in Campylobacter jejuni lacking monofunctional TlyA (which catalyzes the reaction of EC 2.1.1.226), motility, biofilm formation, adhesion to and invasion of human epithelial cells and stimulation of IL-8 production are enhanced above wild-type level
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
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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
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
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
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
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
-
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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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). TLYA_MYCTO
Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh)
268
0
28074
Swiss-Prot
-
TLYA_MYCTU
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
268
0
28074
Swiss-Prot
other Location (Reliability: 4)
A0QYR0_MYCS2
Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155)
269
0
28359
TrEMBL
other Location (Reliability: 1)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
generation of a tlyA deletion mutant
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant C-terminally His-tagged enzyme from Escherichia coli
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
-
gene tlyA, DNA and amino acid sequence determination, analysis and comparison, expression in Escherichia coli strain DH1
-
gene tlyA, DNA and amino acid sequence determination, analysis and comparison, expression in Escherichia coli strain DH1
gene tlyA, DNA and amino acid sequence determination, analysis and comparison, expression in Escherichia coli strain DH1
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
in response to capreomycin, cells downregulate TlyA-mediated methylation of 16S and 23S (cf. EC 2.1.1.226) rRNA resulting in decreased drug susceptibility. 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)
the common resistance mutation A1408G is accompanied by a physiological change that involves increased expression of the tlyA gene
in response to capreomycin, cells downregulate TlyA-mediated methylation of 16S and 23S (cf. EC 2.1.1.226) rRNA resulting in decreased drug susceptibility. 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)
in response to capreomycin, cells downregulate TlyA-mediated methylation of 16S and 23S (cf. EC 2.1.1.226) rRNA resulting in decreased drug susceptibility. 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)
-
-
the common resistance mutation A1408G is accompanied by a physiological change that involves increased expression of the tlyA gene
the common resistance mutation A1408G is accompanied by a physiological change that involves increased expression of the tlyA gene
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-
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
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, Mycobacterium tuberculosis H37Rv, Mycolicibacterium smegmatis (A0QYR0), no activity in Escherichia coli, Streptomyces coelicolor, 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
Salamaszynska-Guz, A.; Serafinska, I.; Bacal, P.; Douthwaite, S.
Virulence properties of Campylobacter jejuni are enhanced by displaying a mycobacterial TlyA methylation pattern in its rRNA
Cell. Microbiol.
22
e13199
2020
Mycolicibacterium smegmatis
brenda
EXTERNAL LINKS (specific for EC-Number 2.1.1.227)
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