CFR_STAAU
ID CFR_STAAU Reviewed; 349 AA.
AC A5HBL2; Q3MQ55;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 12-JUN-2007, sequence version 1.
DT 03-AUG-2022, entry version 72.
DE RecName: Full=Ribosomal RNA large subunit methyltransferase Cfr {ECO:0000255|HAMAP-Rule:MF_01873};
DE EC=2.1.1.224 {ECO:0000255|HAMAP-Rule:MF_01873, ECO:0000269|PubMed:21415317};
DE AltName: Full=23S rRNA (adenine(2503)-C(8))-methyltransferase {ECO:0000255|HAMAP-Rule:MF_01873};
DE AltName: Full=23S rRNA m8A2503 methyltransferase {ECO:0000255|HAMAP-Rule:MF_01873};
GN Name=cfr {ECO:0000255|HAMAP-Rule:MF_01873};
OS Staphylococcus aureus.
OG Plasmid pSCFS3.
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=1280;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=11; PLASMID=pSCFS3;
RX PubMed=16569824; DOI=10.1128/aac.50.4.1156-1163.2006;
RA Kehrenberg C., Schwarz S.;
RT "Distribution of florfenicol resistance genes fexA and cfr among
RT chloramphenicol-resistant Staphylococcus isolates.";
RL Antimicrob. Agents Chemother. 50:1156-1163(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROBABLE FUNCTION, AND ANTIBIOTIC
RP RESISTANCE.
RC STRAIN=CM05;
RX PubMed=17555436; DOI=10.1111/j.1365-2958.2007.05744.x;
RA Toh S.M., Xiong L., Arias C.A., Villegas M.V., Lolans K., Quinn J.,
RA Mankin A.S.;
RT "Acquisition of a natural resistance gene renders a clinical strain of
RT methicillin-resistant Staphylococcus aureus resistant to the synthetic
RT antibiotic linezolid.";
RL Mol. Microbiol. 64:1506-1514(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION IN ANTIBIOTIC RESISTANCE.
RC STRAIN=004-737X;
RX PubMed=18391032; DOI=10.1128/aac.00231-08;
RA Mendes R.E., Deshpande L.M., Castanheira M., DiPersio J., Saubolle M.A.,
RA Jones R.N.;
RT "First report of cfr-mediated resistance to linezolid in human
RT staphylococcal clinical isolates recovered in the United States.";
RL Antimicrob. Agents Chemother. 52:2244-2246(2008).
RN [4]
RP FUNCTION IN ANTIBIOTIC RESISTANCE, AND METHYLTRANSFERASE ACTIVITY.
RC STRAIN=405/2002;
RX PubMed=16091044; DOI=10.1111/j.1365-2958.2005.04754.x;
RA Kehrenberg C., Schwarz S., Jacobsen L., Hansen L.H., Vester B.;
RT "A new mechanism for chloramphenicol, florfenicol and clindamycin
RT resistance: methylation of 23S ribosomal RNA at A2503.";
RL Mol. Microbiol. 57:1064-1073(2005).
RN [5]
RP COFACTOR.
RX PubMed=21916495; DOI=10.1021/ja207327v;
RA Grove T.L., Radle M.I., Krebs C., Booker S.J.;
RT "Cfr and RlmN contain a single [4Fe-4S] cluster, which directs two distinct
RT reactivities for S-adenosylmethionine: methyl transfer by SN2 displacement
RT and radical generation.";
RL J. Am. Chem. Soc. 133:19586-19589(2011).
RN [6]
RP FUNCTION AS A 23S RRNA A2503 METHYLTRANSFERASE, CATALYTIC ACTIVITY, AND
RP REACTION MECHANISM.
RX PubMed=21415317; DOI=10.1126/science.1200877;
RA Grove T.L., Benner J.S., Radle M.I., Ahlum J.H., Landgraf B.J., Krebs C.,
RA Booker S.J.;
RT "A radically different mechanism for S-adenosylmethionine-dependent
RT methyltransferases.";
RL Science 332:604-607(2011).
CC -!- FUNCTION: Specifically methylates position 8 of adenine 2503 in 23S
CC rRNA. Confers resistance to some classes of antibiotics, such as
CC chloramphenicol, florfenicol, clindamycin and linezolid.
CC {ECO:0000255|HAMAP-Rule:MF_01873, ECO:0000269|PubMed:16091044,
CC ECO:0000269|PubMed:18391032, ECO:0000269|PubMed:21415317}.
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:0000255|HAMAP-Rule:MF_01873,
CC ECO:0000269|PubMed:21415317};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01873,
CC ECO:0000269|PubMed:21916495};
CC Note=Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3
CC cysteines and an exchangeable S-adenosyl-L-methionine.
CC {ECO:0000255|HAMAP-Rule:MF_01873, ECO:0000269|PubMed:21916495};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_01873}.
CC -!- MISCELLANEOUS: Reaction proceeds by a ping-pong mechanism involving
CC intermediate methylation of a conserved cysteine residue. In details,
CC the methyl group from one SAM molecule is initially transferred to Cys-
CC 338 in a typical SN2 displacement. Then a 5'-dA radical formed from a
CC second molecule of SAM abstracts a hydrogen from the methyl group of
CC mCys-338, and the resulting Cys-appended methyl radical attacks the
CC substrate adenine ring. Methyl transfer to C8 thus results in a
CC covalent adduct between the substrate and Cys-338, which is resolved by
CC formation of a disulfide bond between Cys-338 and a second conserved
CC Cys residue (Cys-105) (Probable). {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the radical SAM superfamily. RlmN family. Cfr
CC subfamily. {ECO:0000255|HAMAP-Rule:MF_01873}.
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DR EMBL; AM086211; CAJ30491.1; -; Genomic_DNA.
DR EMBL; EF450709; ABQ00063.1; -; Genomic_DNA.
DR EMBL; KC206006; ACC77590.1; -; Genomic_DNA.
DR RefSeq; WP_001010505.1; NZ_VRRS01000001.1.
DR RefSeq; WP_032491462.1; NG_047632.1.
DR RefSeq; YP_007878372.1; NC_021076.1.
DR RefSeq; YP_007988851.1; NC_021230.1.
DR AlphaFoldDB; A5HBL2; -.
DR SMR; A5HBL2; -.
DR GeneID; 64233978; -.
DR BRENDA; 2.1.1.224; 3352.
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_0000350426"
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|HAMAP-Rule:MF_01873"
FT ACT_SITE 338
FT /note="S-methylcysteine intermediate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01873"
FT BINDING 112
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01873"
FT BINDING 116
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01873"
FT BINDING 119
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01873"
FT BINDING 158..159
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01873"
FT BINDING 189
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01873"
FT BINDING 212..214
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01873"
FT BINDING 293
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01873"
FT DISULFID 105..338
FT /note="(transient)"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01873"
FT CONFLICT 254
FT /note="A -> D (in Ref. 1; CAJ30491)"
FT /evidence="ECO:0000305"
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
