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Information on EC 2.1.1.224 - 23S rRNA (adenine2503-C8)-methyltransferase
for references in articles please use BRENDA:EC2.1.1.224
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EC Tree 2 Transferases
2.1 Transferring one-carbon groups
2.1.1 Methyltransferases
2.1.1.224 23S rRNA (adenine2503-C8)-methyltransferase
IUBMB Comments
This enzyme is a member of the ’AdoMet radical’ (radical SAM) family. S-Adenosyl-L-methionine acts as both a radical generator and as the source of the appended methyl group. It contains an [4Fe-4S] cluster [3,6,7]. Cfr is an plasmid-acquired methyltransferase that protects cells from the action of antibiotics . The enzyme methylates adenosine at position 2503 of 23S rRNA by a radical mechanism, transferring a CH2 group from S-adenosyl-L-methionine while retaining the hydrogen at the C-8 position of the adenine. Cfr first transfers an CH2 group to a conserved cysteine (Cys338 in Staphylococcus aureus) , the generated radical from a second S-adenosyl-L-methionine then attacks the methyl group, exctracting a hydrogen. The formed radical forms a covalent intermediate with the adenine group of the tRNA . The enzyme will also methylate 2-methyladenine produced by the action of EC 2.1.1.192 [23S rRNA (adenine2503-C2)-methyltransferase].
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
- 2.1.1.224
- linezolid
-
oxazolidinone
-
5\'-deoxyadenosyl
-
thiopeptide
-
optra
-
linezolid-resistant
-
phenicols
-
cobalamin-dependent
-
phlopsa
-
pleuromutilins
-
nosiheptide
- 5'-deoxyadenosine
-
poxta
-
ribosome-targeting
-
cobiialamin
Reaction Schemes
show2
+
+
2
=
+
+
+
+
2
2
+
adenine2503 in 23S rRNA
+
2
=
+
+
+
8-methyladenine2503 in 23S rRNA
+
2
Synonyms
cfr(c), cfr-like, antibiotic resistance protein, cfr methyltransferase, radical s-adenosylmethionine enzyme, radical-sam enzyme, cfr(e), radical s-adenosylmethionine methylase, cfr-like protein, rs methylase, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
antibiotic resistance protein
Ba Cfr
C8 adenine RNA methylase
Cd Cfr
Cfr
Cfr methyltransferase
Cfr(E)
cfr-like
ClbA
ClbB
EC 2.1.1.194
-
-
formerly, part transferred
-
Ef Cfr
Pl Cfr
radical S-adenosylmethionine methylase
RS methylase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin = S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin = S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
-
-
-
-
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin = S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
the enzyme catalyzes adenosine methylation by using a radical mechanism for substrate activation. The radical chemistry is enabled by the [4Fe-4S] cluster
-
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin = S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
the methyl group is not transferred directly from S-adenosyl-L-methionine to the RNA. Reaction proceeds by a ping-pong mechanism involving intermediate methylation of a conserved cysteine residue
-
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin = S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
enzyme Cfr consumes two AdoMet equivalents per reaction cycle to support both methyl transfer to Cfr Cys338 (AdoMet1, step 1) and subsequently generation of the 59dA. radical (AdoMet2, step2)
-
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin = S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
reaction mechanism modeling overview
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin = S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
the enzyme uses a mechanism involving radical S-adenosyl methionine to methylate RNA via an intermediate with a methylated cysteine in the enzyme and a transient cross-linking to the RNA
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PATHWAY SOURCE
PATHWAYS
MetaCyc
linezolid resistance
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SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:23S rRNA (adenine2503-C8)-methyltransferase
This enzyme is a member of the 'AdoMet radical' (radical SAM) family. S-Adenosyl-L-methionine acts as both a radical generator and as the source of the appended methyl group. It contains an [4Fe-4S] cluster [3,6,7]. Cfr is an plasmid-acquired methyltransferase that protects cells from the action of antibiotics [1]. The enzyme methylates adenosine at position 2503 of 23S rRNA by a radical mechanism, transferring a CH2 group from S-adenosyl-L-methionine while retaining the hydrogen at the C-8 position of the adenine. Cfr first transfers an CH2 group to a conserved cysteine (Cys338 in Staphylococcus aureus) [7], the generated radical from a second S-adenosyl-L-methionine then attacks the methyl group, exctracting a hydrogen. The formed radical forms a covalent intermediate with the adenine group of the tRNA [8]. The enzyme will also methylate 2-methyladenine produced by the action of EC 2.1.1.192 [23S rRNA (adenine2503-C2)-methyltransferase].
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CAS REGISTRY NUMBER
COMMENTARY
39369-30-7
-
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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
2 S-adenosyl-L-methionine + 2-methyladenine2503 in 23S rRNA
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 2,8-dimethyladenine2503 in 23S rRNA
-
Substrates: S-adenosylmethionine is both the methyl donor and the source of a 5'-deoxyadenosyl radical, which activates the substrate for methylation
Products: incubation of Cfr with the wild-type 23S rRNA, already modified at the C2 position by the endogenous RlmN, provides 2,8-dimethyladenosine as the sole product
Products: incubation of Cfr with the wild-type 23S rRNA, already modified at the C2 position by the endogenous RlmN, provides 2,8-dimethyladenosine as the sole product
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA
2 S-adenosyl-L-homocysteine + 2,8-dimethyladenine2503 in 23S rRNA
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [4Fe-4S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [4Fe-4S] ferredoxin
S-adenosyl-L-methionine + adenine2503 in 23S rRNA + reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + oxidized [2Fe-2S] ferredoxin
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA
Substrates: -
Products: verification of RNA methylation at A2503 in 23S rRNA by primer extension method
Products: verification of RNA methylation at A2503 in 23S rRNA by primer extension method
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA
-
Substrates: the enzyme methylates the 8 position of 23S rRNA residue A2503 to confer resistance to multiple antibiotic classes acting upon the large subunit of the bacterial ribosome
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA
-
Substrates: in the presence of sodium dithionite reconstituted Cfr is both reducible and able to cleave S-adenosyl-L-methionine to 5'-deoxyadeonsine, DOA
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA
-
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA
-
Substrates: -
Products: verification of RNA methylation at A2503 in 23S rRNA by primer extension method
Products: verification of RNA methylation at A2503 in 23S rRNA by primer extension method
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA
-
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA
-
Substrates: -
Products: verification of RNA methylation at A2503 in 23S rRNA by primer extension method
Products: verification of RNA methylation at A2503 in 23S rRNA by primer extension method
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA
Substrates: -
Products: verification of RNA methylation at A2503 in 23S rRNA by primer extension method
Products: verification of RNA methylation at A2503 in 23S rRNA by primer extension method
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA
Substrates: -
Products: verification of RNA methylation at A2503 in 23S rRNA by primer extension method
Products: verification of RNA methylation at A2503 in 23S rRNA by primer extension method
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA
-
Substrates: Cfr is an plasmid-acquired methyltransferase that protects cells from the action of antibiotics
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA
-
Substrates: S-adenosylmethionine is both the methyl donor and the source of a 5'-deoxyadenosyl radical, which activates the substrate for methylation. The enzyme can utilize protein-free 23S rRNA as a substrate, but not the fully assembled large ribosomal subunit, suggesting that the methylations take place during the assembly of the ribosome. The key recognition elements in the 23S rRNA are helices 90-92 and the adjacent single stranded RNA that encompasses A2503
Products: identification of the reaction products as 8-methyladenine2503, and 2,8-dimethyladenine2503
Products: identification of the reaction products as 8-methyladenine2503, and 2,8-dimethyladenine2503
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA
-
Substrates: the newly introduced methyl group is assembled from an S-adenosyl-L-methionine (SAM)-derived methylene fragment and a hydrogen atom that had migrated from the substrate amidine carbon. Rather than activating the adenosine nucleotide of the substrate by hydrogen atom abstraction from an amidine carbon, the 5'-deoxyadenosyl radical abstracts hydrogen from the second equivalent of SAM to form the SAM-derived radical cation. This species, or its corresponding sulfur ylide, subsequently adds into the substrate, initiating hydride shift and S-adenosylhomocysteine elimination to complete the formation of the methyl group
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA
-
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA
-
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
-
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
-
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
-
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
-
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
-
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
Paenibacillus lautus Y412MC10
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
-
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [4Fe-4S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [4Fe-4S] ferredoxin
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [4Fe-4S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [4Fe-4S] ferredoxin
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [4Fe-4S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [4Fe-4S] ferredoxin
-
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [4Fe-4S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [4Fe-4S] ferredoxin
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [4Fe-4S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [4Fe-4S] ferredoxin
-
Substrates: enzyme Cfr consumes two AdoMet equivalents per reaction cycle to support both methyl transfer to Cfr Cys338 (AdoMet1, step 1) and subsequently generation of the 59dA. radical (AdoMet2, step2)
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [4Fe-4S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [4Fe-4S] ferredoxin
Substrates: two S-adenosyl-L-methionine molecules serve as the cofactor by providing the 5'-deoxyadenosyl radical for substrate activation and the methyl
Products: -
Products: -
?
additional information
?
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Substrates: kinetic analysis of methylation of a 155mer rRNA substrate by Cfr enzymes under limiting and under excess substrate conditions initiated with a protein-based reductant, substrate sequence, overview
Products: -
Products: -
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additional information
?
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Substrates: kinetic analysis of methylation of a 155mer rRNA substrate by Cfr enzymes under limiting and under excess substrate conditions initiated with a protein-based reductant, substrate sequence, overview
Products: -
Products: -
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additional information
?
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Substrates: in vitro assays with Escherichia coli RNA
Products: -
Products: -
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additional information
?
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Substrates: kinetic analysis of methylation of a 155mer rRNA substrate by Cfr enzymes under limiting and under excess substrate conditions initiated with a protein-based reductant, substrate sequence, overview
Products: -
Products: -
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additional information
?
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Substrates: in vitro assays with Escherichia coli RNA
Products: -
Products: -
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additional information
?
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Substrates: kinetic analysis of methylation of a 155mer rRNA substrate by Cfr enzymes under limiting and under excess substrate conditions initiated with a protein-based reductant, substrate sequence, overview
Products: -
Products: -
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additional information
?
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Substrates: kinetic analysis of methylation of a 155mer rRNA substrate by Cfr enzymes under limiting and under excess substrate conditions initiated with a protein-based reductant, substrate sequence, overview
Products: -
Products: -
-
additional information
?
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Substrates: kinetic analysis of methylation of a 155mer rRNA substrate by Cfr enzymes under limiting and under excess substrate conditions initiated with a protein-based reductant, substrate sequence, overview
Products: -
Products: -
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additional information
?
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Substrates: Cfr confers a phenotype with resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins, and streptogramin A antibiotics. Methylation of position 8 is the dominant antibiotic resistance determinant, but indigenous modification at position 2 also contributes to low-level resistance
Products: -
Products: -
?
additional information
?
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Substrates: Cfr methylates A2503 of 23S rRNA at C8 and C2, while RlmN only performs a C2 methylation using the same mechanism of function
Products: -
Products: -
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additional information
?
-
Substrates: kinetic analysis of methylation of a 155mer rRNA substrate by Cfr enzymes under limiting and under excess substrate conditions initiated with a protein-based reductant, substrate sequence, overview
Products: -
Products: -
-
additional information
?
-
Paenibacillus lautus Y412MC10
Substrates: kinetic analysis of methylation of a 155mer rRNA substrate by Cfr enzymes under limiting and under excess substrate conditions initiated with a protein-based reductant, substrate sequence, overview
Products: -
Products: -
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additional information
?
-
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Substrates: enzyme Cfr methylates adenosine 2503 of the 23S rRNA in the peptidyltransferase centre (P-site) of the bacterial ribosome. In wild-type Cfr, where Cys338 is methylated, S-adenosyl-L-methionine binding leads to rapid oxidation of the [4Fe-4S] cluster and production of 5'-deoxyadenosine
Products: -
Products: -
?
additional information
?
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Substrates: methylation at C8 is similar to that at C2, cf. EC 2.1.1.192
Products: -
Products: -
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additional information
?
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Substrates: the enzyme employs a [4Fe-4S] cluster to supply the requisite electron for reductive cleavage of SAM, usually to L-methionine and a 5'-deoxyadenosyl 5'-radical. SAM is the source of both the 5'-deoxyadenosyl 5'-radical and the appended methyl group
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
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [4Fe-4S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [4Fe-4S] ferredoxin
S-adenosyl-L-methionine + adenine2503 in 23S rRNA + reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + oxidized [2Fe-2S] ferredoxin
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA
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Substrates: the enzyme methylates the 8 position of 23S rRNA residue A2503 to confer resistance to multiple antibiotic classes acting upon the large subunit of the bacterial ribosome
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA
-
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA
-
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA
-
Substrates: Cfr is an plasmid-acquired methyltransferase that protects cells from the action of antibiotics
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA
-
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA
-
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
-
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
-
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
-
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
-
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
-
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
Paenibacillus lautus Y412MC10
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
-
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [4Fe-4S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [4Fe-4S] ferredoxin
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [4Fe-4S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [4Fe-4S] ferredoxin
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [4Fe-4S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [4Fe-4S] ferredoxin
-
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [4Fe-4S] ferredoxin
S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [4Fe-4S] ferredoxin
Substrates: -
Products: -
Products: -
?
additional information
?
-
Substrates: Cfr confers a phenotype with resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins, and streptogramin A antibiotics. Methylation of position 8 is the dominant antibiotic resistance determinant, but indigenous modification at position 2 also contributes to low-level resistance
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme Cfr methylates adenosine 2503 of the 23S rRNA in the peptidyltransferase centre (P-site) of the bacterial ribosome. In wild-type Cfr, where Cys338 is methylated, S-adenosyl-L-methionine binding leads to rapid oxidation of the [4Fe-4S] cluster and production of 5'-deoxyadenosine
Products: -
Products: -
?
additional information
?
-
Substrates: methylation at C8 is similar to that at C2, cf. EC 2.1.1.192
Products: -
Products: -
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ferredoxin
-
enzyme Cfr contains a single [4Fe-4S] cluster that binds two separate molecules of S-adenosyl-L-methionine during the reaction cycle
-
S-adenosyl-L-methionine
-
enzyme Cfr contains a single [4Fe-4S] cluster that binds two separate molecules of S-adenosyl-L-methionine during the reaction cycle
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Fe-S-clusters
-
contains a 4Fe-4S cluster. Radical-SAM enzymes contain a [4Fe-4S]+ cluster that is coordinated by the three conserved cysteine thiolate side chains in the CX3CX2C motif and one molecule of S-adenosyl-L-methionine
Fe2+
Mg2+
Fe2+
-
4Fe-4S cluster. Fe-S clusters are of structural, as well as functional, importance to Cfr. Radical-SAM enzymes use an Fe-S cluster to generate the 5'-deoxyadenosyl radical from SAM, enabling them to modify intrinsically unreactive centres such as adenosine C8. Anaerobic purification from Azotobacter vinelandii Cfr
Fe2+
Clostridioides difficile Cfr contains an additional Cys-rich C-terminal domain that binds a mononuclear Fe2+ ion in a rubredoxin-type Cys4 motif. The rate of turnover is decreased upon disruption of the Fe2+-binding site by Zn2+ substitution or ligand mutation
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Dehydration
Mechanism of Diol Dehydration by a Promiscuous Radical-SAM Enzyme Homologue of the Antiviral Enzyme Viperin (RSAD2).
Infections
Genomic Analysis of Emerging Florfenicol-Resistant Campylobacter coli Isolated from the Cecal Contents of Cattle in the United States.
Tuberculosis
The crystal structure of Rv1347c, a putative antibiotic resistance protein from Mycobacterium tuberculosis, reveals a GCN5-related fold and suggests an alternative function in siderophore biosynthesis.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
kinetic analysis, overview
-
additional information
additional information
kinetic analysis, overview
-
additional information
additional information
kinetic analysis, overview
-
additional information
additional information
kinetic analysis, overview
-
additional information
additional information
energy profile and thermodynamics, overview
-
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
or strain domuvar, gene clbC, a cfr-like gene
UniProt
brenda