TSRM_STRLU
ID TSRM_STRLU Reviewed; 599 AA.
AC C0JRZ9;
DT 20-JAN-2016, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 1.
DT 03-AUG-2022, entry version 45.
DE RecName: Full=Tryptophan 2-C-methyltransferase {ECO:0000305};
DE EC=2.1.1.106 {ECO:0000269|PubMed:23064318};
GN Name=tsrM {ECO:0000303|PubMed:19265401}; Synonyms=trsT;
OS Streptomyces laurentii.
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=39478;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=ATCC 31255;
RX PubMed=19246004; DOI=10.1016/j.chembiol.2009.01.007;
RA Liao R., Duan L., Lei C., Pan H., Ding Y., Zhang Q., Chen D., Shen B.,
RA Yu Y., Liu W.;
RT "Thiopeptide biosynthesis featuring ribosomally synthesized precursor
RT peptides and conserved posttranslational modifications.";
RL Chem. Biol. 16:141-147(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=ATCC 31255;
RX PubMed=19265401; DOI=10.1021/ja807890a;
RA Kelly W.L., Pan L., Li C.;
RT "Thiostrepton biosynthesis: prototype for a new family of bacteriocins.";
RL J. Am. Chem. Soc. 131:4327-4334(2009).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF CYS-253; CYS-257 AND CYS-260,
RP COFACTOR, AND REACTION MECHANISM.
RX PubMed=23064318; DOI=10.1038/nchembio.1091;
RA Pierre S., Guillot A., Benjdia A., Sandstroem C., Langella P., Berteau O.;
RT "Thiostrepton tryptophan methyltransferase expands the chemistry of radical
RT SAM enzymes.";
RL Nat. Chem. Biol. 8:957-959(2012).
CC -!- FUNCTION: Involved in the biosynthetic pathway of the antibiotic
CC thiostrepton A. First, TsrM catalyzes the transfer of a methyl group
CC from S-adenosyl methionine (SAM) to cobalamin, leading to the formation
CC of methylcobalamin (CH3-cobalamin) and S-adenosyl-L-homocysteine (SAH).
CC Then the methyl group is transferred to the C2 position of tryptophan
CC (Trp) with the concerted action of the radical SAM [4Fe-4S] center,
CC leading to the production of methyltryptophan.
CC {ECO:0000269|PubMed:19246004, ECO:0000269|PubMed:19265401,
CC ECO:0000269|PubMed:23064318}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-tryptophan + S-adenosyl-L-methionine = 2-methyl-L-tryptophan
CC + H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:17321,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:57912,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:85908; EC=2.1.1.106;
CC Evidence={ECO:0000269|PubMed:23064318};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000269|PubMed:23064318};
CC Note=Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3
CC cysteines and an exchangeable S-adenosyl-L-methionine.
CC {ECO:0000269|PubMed:23064318};
CC -!- COFACTOR:
CC Name=cob(II)alamin; Xref=ChEBI:CHEBI:16304;
CC Evidence={ECO:0000269|PubMed:23064318};
CC -!- MISCELLANEOUS: TsrM has a totally new mechanism among
CC methyltransferases and radical SAM enzymes. TsrM is not able to use
CC methylcobalamin directly but instead coordinates free cobalamin. SAM
CC serves exclusively as a methyl donor and not as a radical source, and
CC the methyl group of SAM is not directly transferred to tryptophan.
CC {ECO:0000269|PubMed:23064318}.
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DR EMBL; FJ652572; ACN52303.1; -; Genomic_DNA.
DR EMBL; FJ436358; ACN80682.1; -; Genomic_DNA.
DR AlphaFoldDB; C0JRZ9; -.
DR SMR; C0JRZ9; -.
DR KEGG; ag:ACN52303; -.
DR BioCyc; MetaCyc:MON-19353; -.
DR BRENDA; 2.1.1.106; 6048.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0031419; F:cobalamin binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0030772; F:tryptophan 2-C-methyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR Gene3D; 3.80.30.20; -; 1.
DR InterPro; IPR030969; B12_rSAM_trp_MT.
DR InterPro; IPR006158; Cobalamin-bd.
DR InterPro; IPR006638; Elp3/MiaB/NifB.
DR InterPro; IPR007197; rSAM.
DR InterPro; IPR023404; rSAM_horseshoe.
DR Pfam; PF02310; B12-binding; 1.
DR Pfam; PF04055; Radical_SAM; 1.
DR SFLD; SFLDF00322; tryptophan_2-C-methyltransfera; 1.
DR SMART; SM00729; Elp3; 1.
DR TIGRFAMs; TIGR04428; B12_rSAM_trp_MT; 1.
DR PROSITE; PS51332; B12_BINDING; 1.
DR PROSITE; PS51918; RADICAL_SAM; 1.
PE 1: Evidence at protein level;
KW 4Fe-4S; Antibiotic biosynthesis; Cobalamin; Cobalt; Iron; Iron-sulfur;
KW Metal-binding; S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..599
FT /note="Tryptophan 2-C-methyltransferase"
FT /id="PRO_0000435308"
FT DOMAIN 4..149
FT /note="B12-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00666"
FT DOMAIN 239..492
FT /note="Radical SAM core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01266"
FT REGION 167..197
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 174..196
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 253
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000269|PubMed:23064318"
FT BINDING 257
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000269|PubMed:23064318"
FT BINDING 260
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000269|PubMed:23064318"
FT MUTAGEN 253
FT /note="C->A: Loss of methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:23064318"
FT MUTAGEN 257
FT /note="C->A: Loss of methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:23064318"
FT MUTAGEN 260
FT /note="C->A: Loss of methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:23064318"
SQ SEQUENCE 599 AA; 66061 MW; A3829A2EEE2C851A CRC64;
MLRKGTVALI NPNQIHPPIA PYALDVLTTA LEASGFEAHV LDLTFHLDDW RQTLRDYFRA
ERPLLVGVTC RNTDTVYALE QRPFVDGYKA VIDEVRRLTA APVVAGGVGF STMPFALVDY
FGIEYGVKGP GEKIICDLAR ALAEGRSADR IHIPGLLVNR GPGNVTRVAP PALDPRAAPA
PSSSPSPSPA PSSSSAPVPV PLSFAAVGHH ESRAWQAETE LPYTRRSGEP YKVDNLRYYR
EGGLGSILTK NGCVYKCSFC VEPDAKGTQF ARRGITAVVD EMEALTAQGI HDLHTTDSEF
NLSIAHSKNL LREIVRRRDH DATSPLRDLR LWVYCQPSPF DEEFAELLAA AGCAGVNIGA
DHTRPEMLDG WKVTAKGTRY YDFADTERLV QLCHRNGMLT MVEALFGMPG ETLETMRDCV
DRMMELDATV TGFSLGLRLL PYMGLAKSLA EQCDGVRTVR GLQSNNASGP IVLKQLHQCD
GPIEYERQFM FDESGDFRLV CYFSPDLPEA PGTADSPDGI WRASVDFLWD RIPKSEQYRV
MLPTLSGSSE NDNNYADNPF LTSLNRKGYT GAFWAHWRDR EAIMSGATLP LGELAEAVR
