ERM_BACIU
ID ERM_BACIU Reviewed; 244 AA.
AC P13956;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=rRNA adenine N-6-methyltransferase;
DE EC=2.1.1.184;
DE AltName: Full=Erythromycin resistance protein;
DE AltName: Full=Macrolide-lincosamide-streptogramin B resistance protein;
GN Name=ermC';
OS Bacillus subtilis.
OG Plasmid pIM13.
OC Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Bacillus.
OX NCBI_TaxID=1423;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3087948; DOI=10.1128/jb.167.1.138-147.1986;
RA Monod M., Denoya C., Dubnau D.;
RT "Sequence and properties of pIM13, a macrolide-lincosamide-streptogramin B
RT resistance plasmid from Bacillus subtilis.";
RL J. Bacteriol. 167:138-147(1986).
RN [2]
RP CHARACTERIZATION.
RX PubMed=7543473; DOI=10.1128/jb.177.15.4327-4332.1995;
RA Zhong P., Pratt S.D., Edalji R.P., Walter K.A., Holzman T.F.,
RA Shivakumar A.G., Katz L.;
RT "Substrate requirements for ErmC' methyltransferase activity.";
RL J. Bacteriol. 177:4327-4332(1995).
RN [3]
RP MUTAGENESIS OF ASN-101; TYR-104; PRO-165 AND LYS-166, RNA-BINDING, AND
RP FUNCTION.
RX PubMed=12946350; DOI=10.1016/s0022-2836(03)00863-5;
RA Maravic G., Feder M., Pongor S., Floegel M., Bujnicki J.M.;
RT "Mutational analysis defines the roles of conserved amino acid residues in
RT the predicted catalytic pocket of the rRNA:m6A methyltransferase ErmC'.";
RL J. Mol. Biol. 332:99-109(2003).
RN [4]
RP MUTAGENESIS OF THR-108; ARG-112; LYS-133; ARG-134 AND ARG-140, RNA-BINDING,
RP AND FUNCTION.
RX PubMed=12907737; DOI=10.1093/nar/gkg666;
RA Maravic G., Bujnicki J.M., Feder M., Pongor S., Floegel M.;
RT "Alanine-scanning mutagenesis of the predicted rRNA-binding domain of ErmC'
RT redefines the substrate-binding site and suggests a model for protein-RNA
RT interactions.";
RL Nucleic Acids Res. 31:4941-4949(2003).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 10-244.
RC STRAIN=BD1109;
RX PubMed=9585521; DOI=10.1021/bi973113c;
RA Bussiere D.E., Muchmore S.W., Dealwis C.G., Schluckebier G., Nienaber V.L.,
RA Edalji R.P., Walter K.A., Ladror U.S., Holzman T.F., Abad-Zapatero C.;
RT "Crystal structure of ErmC', an rRNA methyltransferase which mediates
RT antibiotic resistance in bacteria.";
RL Biochemistry 37:7103-7112(1998).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEXES WITH
RP S-ADENOSYL-L-METHIONINE AND SUBSTRATE ANALOGS.
RX PubMed=10366505; DOI=10.1006/jmbi.1999.2788;
RA Schluckebier G., Zhong P., Stewart K.D., Kavanaugh T.J., Abad-Zapatero C.;
RT "The 2.2-A structure of the rRNA methyltransferase ErmC' and its complexes
RT with cofactor and cofactor analogs: implications for the reaction
RT mechanism.";
RL J. Mol. Biol. 289:277-291(1999).
CC -!- FUNCTION: This protein produces a dimethylation of the adenine residue
CC at position 2085 in 23S rRNA, resulting in reduced affinity between
CC ribosomes and macrolide-lincosamide-streptogramin B antibiotics.
CC {ECO:0000269|PubMed:12907737, ECO:0000269|PubMed:12946350}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=adenosine(2085) in 23S rRNA + 2 S-adenosyl-L-methionine = 2
CC H(+) + N(6)-dimethyladenosine(2085) in 23S rRNA + 2 S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:42784, Rhea:RHEA-COMP:10237, Rhea:RHEA-
CC COMP:10238, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:74411, ChEBI:CHEBI:74493; EC=2.1.1.184;
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. rRNA adenine N(6)-methyltransferase family.
CC {ECO:0000255|PROSITE-ProRule:PRU01026}.
CC -!- CAUTION: In the genome of Neisseria meningitidis (serogroup B), the
CC gene for this protein is present (NMB0066). It was introduced as part
CC of a construct built to neutralize the virulence of the bacterium.
CC {ECO:0000305}.
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DR EMBL; M13761; AAA98136.1; -; Genomic_DNA.
DR PIR; B25233; B25233.
DR RefSeq; NP_040407.1; NC_001376.1.
DR RefSeq; WP_001003263.1; NG_047806.1.
DR PDB; 1QAM; X-ray; 2.20 A; A=1-244.
DR PDB; 1QAN; X-ray; 2.40 A; A=1-244.
DR PDB; 1QAO; X-ray; 2.70 A; A=1-244.
DR PDB; 1QAQ; X-ray; 2.80 A; A=1-244.
DR PDB; 2ERC; X-ray; 3.03 A; A/B=1-244.
DR PDBsum; 1QAM; -.
DR PDBsum; 1QAN; -.
DR PDBsum; 1QAO; -.
DR PDBsum; 1QAQ; -.
DR PDBsum; 2ERC; -.
DR AlphaFoldDB; P13956; -.
DR SMR; P13956; -.
DR BindingDB; P13956; -.
DR ChEMBL; CHEMBL4251; -.
DR DrugBank; DB01752; S-adenosyl-L-homocysteine.
DR DrugBank; DB01910; Sinefungin.
DR KEGG; ag:AAA98136; -.
DR BRENDA; 2.1.1.184; 658.
DR SABIO-RK; P13956; -.
DR EvolutionaryTrace; P13956; -.
DR PRO; PR:P13956; -.
DR GO; GO:0052910; F:23S rRNA (adenine(2085)-N(6))-dimethyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0000179; F:rRNA (adenine-N6,N6-)-dimethyltransferase activity; IEA:InterPro.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR Gene3D; 1.10.8.100; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR001737; KsgA/Erm.
DR InterPro; IPR023165; rRNA_Ade_diMease-like_C.
DR InterPro; IPR020596; rRNA_Ade_Mease_Trfase_CS.
DR InterPro; IPR020598; rRNA_Ade_methylase_Trfase_N.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR11727; PTHR11727; 1.
DR Pfam; PF00398; RrnaAD; 1.
DR SMART; SM00650; rADc; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS01131; RRNA_A_DIMETH; 1.
DR PROSITE; PS51689; SAM_RNA_A_N6_MT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic resistance; Methyltransferase; Plasmid;
KW RNA-binding; S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..244
FT /note="rRNA adenine N-6-methyltransferase"
FT /id="PRO_0000101674"
FT BINDING 11
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 13
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 38
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 59
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 84
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 101
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT MUTAGEN 11
FT /note="N->A: Reduces activity about 3-fold."
FT MUTAGEN 101
FT /note="N->A: Decreases affinity for S-adenosyl-L-methionine
FT 4-fold. Reduces activity by 90%."
FT /evidence="ECO:0000269|PubMed:12946350"
FT MUTAGEN 104
FT /note="Y->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:12946350"
FT MUTAGEN 108
FT /note="T->A: Decreases affinity for S-adenosyl-L-methionine
FT 8-fold. Reduces activity by 99%."
FT /evidence="ECO:0000269|PubMed:12907737"
FT MUTAGEN 112
FT /note="R->A: Reduces activity by 90%."
FT /evidence="ECO:0000269|PubMed:12907737"
FT MUTAGEN 112
FT /note="R->D: Decreases affinity for S-adenosyl-L-methionine
FT 5-fold. Decreases affinity for RNA 6-fold. Reduces activity
FT by 99%."
FT /evidence="ECO:0000269|PubMed:12907737"
FT MUTAGEN 133
FT /note="K->A: Reduces activity by about 80%."
FT /evidence="ECO:0000269|PubMed:12907737"
FT MUTAGEN 134
FT /note="R->A: Decreases affinity for S-adenosyl-L-methionine
FT 7-fold. Decreases affinity for RNA about 4-fold. Reduces
FT activity by over 99%. May severely impair protein folding."
FT /evidence="ECO:0000269|PubMed:12907737"
FT MUTAGEN 140
FT /note="R->A: Decreases affinity for S-adenosyl-L-methionine
FT 7-fold. Reduces activity by about 85%."
FT /evidence="ECO:0000269|PubMed:12907737"
FT MUTAGEN 165
FT /note="P->A: Decreases affinity for S-adenosyl-L-methionine
FT 6-fold. Reduces activity by about 96%."
FT /evidence="ECO:0000269|PubMed:12946350"
FT MUTAGEN 166
FT /note="K->A: Decreases affinity for RNA about 6-fold."
FT /evidence="ECO:0000269|PubMed:12946350"
FT HELIX 16..23
FT /evidence="ECO:0007829|PDB:1QAM"
FT STRAND 33..37
FT /evidence="ECO:0007829|PDB:1QAM"
FT HELIX 43..51
FT /evidence="ECO:0007829|PDB:1QAM"
FT STRAND 52..58
FT /evidence="ECO:0007829|PDB:1QAM"
FT HELIX 62..71
FT /evidence="ECO:0007829|PDB:1QAM"
FT TURN 72..74
FT /evidence="ECO:0007829|PDB:1QAM"
FT STRAND 77..81
FT /evidence="ECO:0007829|PDB:1QAM"
FT HELIX 85..87
FT /evidence="ECO:0007829|PDB:1QAM"
FT STRAND 92..94
FT /evidence="ECO:0007829|PDB:1QAN"
FT STRAND 97..101
FT /evidence="ECO:0007829|PDB:1QAM"
FT HELIX 104..106
FT /evidence="ECO:0007829|PDB:1QAM"
FT HELIX 107..116
FT /evidence="ECO:0007829|PDB:1QAM"
FT STRAND 121..128
FT /evidence="ECO:0007829|PDB:1QAM"
FT HELIX 129..135
FT /evidence="ECO:0007829|PDB:1QAM"
FT STRAND 138..140
FT /evidence="ECO:0007829|PDB:2ERC"
FT HELIX 141..146
FT /evidence="ECO:0007829|PDB:1QAM"
FT TURN 147..149
FT /evidence="ECO:0007829|PDB:1QAM"
FT STRAND 150..158
FT /evidence="ECO:0007829|PDB:1QAM"
FT HELIX 160..162
FT /evidence="ECO:0007829|PDB:1QAM"
FT STRAND 163..165
FT /evidence="ECO:0007829|PDB:1QAM"
FT STRAND 171..178
FT /evidence="ECO:0007829|PDB:1QAM"
FT HELIX 185..187
FT /evidence="ECO:0007829|PDB:1QAM"
FT HELIX 188..199
FT /evidence="ECO:0007829|PDB:1QAM"
FT HELIX 203..205
FT /evidence="ECO:0007829|PDB:1QAM"
FT HELIX 209..219
FT /evidence="ECO:0007829|PDB:1QAM"
FT HELIX 229..242
FT /evidence="ECO:0007829|PDB:1QAM"
SQ SEQUENCE 244 AA; 28907 MW; FC7CA6524034D820 CRC64;
MNEKNIKHSQ NFITSKHNID KIMTNIRLNE HDNIFEIGSG KGHFTLELVQ RCNFVTAIEI
DHKLCKTTEN KLVDHDNFQV LNKDILQFKF PKNQSYKIFG NIPYNISTDI IRKIVFDSIA
DEIYLIVEYG FAKRLLNTKR SLALFLMAEV DISILSMVPR EYFHPKPKVN SSLIRLNRKK
SRISHKDKQK YNYFVMKWVN KEYKKIFTKN QFNNSLKHAG IDDLNNISFE QFLSLFNSYK
LFNK
