CFR_MAMSC
ID CFR_MAMSC Reviewed; 349 AA.
AC Q9FBG4;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 100.
DE RecName: Full=Ribosomal RNA large subunit methyltransferase Cfr;
DE EC=2.1.1.224 {ECO:0000269|PubMed:19144912};
DE AltName: Full=23S rRNA (adenine(2503)-C(8))-methyltransferase;
DE AltName: Full=23S rRNA m8A2503 methyltransferase;
GN Name=cfr;
OS Mammaliicoccus sciuri (Staphylococcus sciuri).
OG Plasmid pSCFS1.
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Mammaliicoccus.
OX NCBI_TaxID=1296;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION IN ANTIBIOTIC RESISTANCE.
RC STRAIN=5233/34;
RX PubMed=10952608; DOI=10.1128/aac.44.9.2530-2533.2000;
RA Schwarz S., Werckenthin C., Kehrenberg C.;
RT "Identification of a plasmid-borne chloramphenicol-florfenicol resistance
RT gene in Staphylococcus sciuri.";
RL Antimicrob. Agents Chemother. 44:2530-2533(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=15471995; DOI=10.1093/jac/dkh457;
RA Kehrenberg C., Ojo K.K., Schwarz S.;
RT "Nucleotide sequence and organization of the multiresistance plasmid pSCFS1
RT from Staphylococcus sciuri.";
RL J. Antimicrob. Chemother. 54:936-939(2004).
RN [3]
RP FUNCTION AS A METHYLTRANSFERASE, CATALYTIC ACTIVITY, ANTIBIOTIC RESISTANCE,
RP AND MUTAGENESIS OF CYS-110; CYS-112; CYS-116 AND CYS-119.
RX PubMed=19144912; DOI=10.1261/rna.1371409;
RA Giessing A.M.B., Jensen S.S., Rasmussen A., Hansen L.H., Gondela A.,
RA Long K., Vester B., Kirpekar F.;
RT "Identification of 8-methyladenosine as the modification catalyzed by the
RT radical SAM methyltransferase Cfr that confers antibiotic resistance in
RT bacteria.";
RL RNA 15:327-336(2009).
CC -!- FUNCTION: Specifically methylates position 8 of adenine 2503 in 23S
CC rRNA. Can also methylate position 2 of A2503 after the primary
CC methylation at position 8 is complete, to form 2,8-dimethyladenosine;
CC however, C8 is its preferred target. Confers resistance to several
CC classes of antibiotics such as phenicols, lincosamides, oxazolidinones,
CC pleuromutilins, and streptogramin A. The antibiotic resistance
CC conferred by Cfr is provided by methylation at the 8 position and is
CC independent of methylation at the 2 position of A2503.
CC {ECO:0000269|PubMed:10952608, ECO:0000269|PubMed:19144912}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=adenosine(2503) in 23S rRNA + 2 reduced [2Fe-2S]-[ferredoxin]
CC + 2 S-adenosyl-L-methionine = 5'-deoxyadenosine + 8-
CC methyladenosine(2503) in 23S rRNA + L-methionine + 2 oxidized [2Fe-
CC 2S]-[ferredoxin] + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:42632,
CC Rhea:RHEA-COMP:10000, Rhea:RHEA-COMP:10001, Rhea:RHEA-COMP:10152,
CC Rhea:RHEA-COMP:10153, ChEBI:CHEBI:17319, ChEBI:CHEBI:33737,
CC ChEBI:CHEBI:33738, ChEBI:CHEBI:57844, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:74411, ChEBI:CHEBI:74543;
CC EC=2.1.1.224; Evidence={ECO:0000269|PubMed:19144912};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; Evidence={ECO:0000250};
CC Note=Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3
CC cysteines and an exchangeable S-adenosyl-L-methionine. {ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- MISCELLANEOUS: Reaction proceeds by a ping-pong mechanism involving
CC intermediate methylation of a conserved cysteine residue.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the radical SAM superfamily. RlmN family. Cfr
CC subfamily. {ECO:0000305}.
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DR EMBL; AJ249217; CAC04525.1; -; Genomic_DNA.
DR EMBL; AJ579365; CAE18142.1; -; Genomic_DNA.
DR RefSeq; NP_899167.1; NC_005076.1.
DR RefSeq; WP_001010505.1; NZ_KX982171.1.
DR AlphaFoldDB; Q9FBG4; -.
DR SMR; Q9FBG4; -.
DR GeneID; 64233978; -.
DR KEGG; ag:CAE18142; -.
DR BioCyc; MetaCyc:MON-16695; -.
DR BRENDA; 2.1.1.192; 8685.
DR BRENDA; 2.1.1.224; 8685.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-UniRule.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016433; F:rRNA (adenine) methyltransferase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0019843; F:rRNA binding; IEA:UniProtKB-UniRule.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR GO; GO:0070475; P:rRNA base methylation; IEA:UniProtKB-UniRule.
DR Gene3D; 3.20.20.70; -; 1.
DR HAMAP; MF_01873; 23SrRNA_methyltr_Cfr; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR040072; Methyltransferase_A.
DR InterPro; IPR022881; rRNA_lsu_MeTfrase_Cfr.
DR InterPro; IPR004383; rRNA_lsu_MTrfase_RlmN/Cfr.
DR InterPro; IPR007197; rSAM.
DR PANTHER; PTHR30544; PTHR30544; 1.
DR Pfam; PF04055; Radical_SAM; 1.
DR PIRSF; PIRSF006004; CHP00048; 1.
DR SFLD; SFLDF00275; adenosine_C2_methyltransferase; 1.
DR SFLD; SFLDF00296; adenosine_C8_methyltransferase; 1.
DR SFLD; SFLDS00029; Radical_SAM; 2.
DR TIGRFAMs; TIGR04432; rSAM_Cfr; 1.
DR PROSITE; PS51918; RADICAL_SAM; 1.
PE 1: Evidence at protein level;
KW 4Fe-4S; Antibiotic resistance; Cytoplasm; Disulfide bond; Iron;
KW Iron-sulfur; Metal-binding; Methyltransferase; Plasmid; rRNA processing;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..349
FT /note="Ribosomal RNA large subunit methyltransferase Cfr"
FT /id="PRO_0000350445"
FT DOMAIN 98..333
FT /note="Radical SAM core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01266"
FT ACT_SITE 91
FT /note="Proton acceptor"
FT /evidence="ECO:0000255"
FT ACT_SITE 338
FT /note="S-methylcysteine intermediate"
FT /evidence="ECO:0000250"
FT BINDING 112
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000305"
FT BINDING 116
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000305"
FT BINDING 119
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000305"
FT BINDING 158..159
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 189
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 212..214
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 293
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT DISULFID 105..338
FT /note="(transient)"
FT /evidence="ECO:0000250"
FT MUTAGEN 110
FT /note="C->A: No change in activity."
FT /evidence="ECO:0000269|PubMed:19144912"
FT MUTAGEN 112
FT /note="C->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:19144912"
FT MUTAGEN 116
FT /note="C->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:19144912"
FT MUTAGEN 119
FT /note="C->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:19144912"
SQ SEQUENCE 349 AA; 39862 MW; 53C5F48D61BE94CD CRC64;
MNFNNKTKYG KIQEFLRSNN EPDYRIKQIT NAIFKQRISR FEDMKVLPKL LREDLINNFG
ETVLNIKLLA EQNSEQVTKV LFEVSKNERV ETVNMKYKAG WESFCISSQC GCNFGCKFCA
TGDIGLKKNL TVDEITDQVL YFHLLGHQID SISFMGMGEA LANRQVFDAL DSFTDPNLFA
LSPRRLSIST IGIIPSIKKI TQEYPQVNLT FSLHSPYSEE RSKLMPINDR YPIDEVMNIL
DEHIRLTSRK VYIAYIMLPG VNDSLEHANE VVSLLKSRYK SGKLYHVNLI RYNPTISAPE
MYGEANEGQV EAFYKVLKSA GIHVTIRSQF GIDIDAACGQ LYGNYQNSQ
