SFMD_STRLA
ID SFMD_STRLA Reviewed; 365 AA.
AC B0CN28;
DT 29-OCT-2014, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 1.
DT 03-AUG-2022, entry version 34.
DE RecName: Full=3-methyl-L-tyrosine peroxygenase {ECO:0000305};
DE EC=1.11.2.5 {ECO:0000269|PubMed:22187429};
GN Name=sfmD {ECO:0000303|PubMed:17981978};
OS Streptomyces lavendulae.
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=1914 {ECO:0000312|EMBL:ABI22134.1};
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=NRRL 11002 {ECO:0000312|EMBL:ABI22134.1};
RX PubMed=17981978; DOI=10.1128/jb.00826-07;
RA Li L., Deng W., Song J., Ding W., Zhao Q.F., Peng C., Song W.W., Tang G.L.,
RA Liu W.;
RT "Characterization of the saframycin A gene cluster from Streptomyces
RT lavendulae NRRL 11002 revealing a nonribosomal peptide synthetase system
RT for assembling the unusual tetrapeptidyl skeleton in an iterative manner.";
RL J. Bacteriol. 190:251-263(2008).
RN [2]
RP FUNCTION, AND PATHWAY.
RX PubMed=19494690; DOI=10.4014/jmb.0808.484;
RA Fu C.Y., Tang M.C., Peng C., Li L., He Y.L., Liu W., Tang G.L.;
RT "Biosynthesis of 3-hydroxy-5-methyl-o-methyltyrosine in the saframycin/
RT safracin biosynthetic pathway.";
RL J. Microbiol. Biotechnol. 19:439-446(2009).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, PATHWAY, AND MUTAGENESIS OF
RP HIS-191; HIS-274; HIS-313 AND CYS-317.
RX PubMed=22187429; DOI=10.1074/jbc.m111.306316;
RA Tang M.C., Fu C.Y., Tang G.L.;
RT "Characterization of SfmD as a heme peroxidase that catalyzes the
RT regioselective hydroxylation of 3-methyltyrosine to 3-hydroxy-5-
RT methyltyrosine in saframycin A biosynthesis.";
RL J. Biol. Chem. 287:5112-5121(2012).
CC -!- FUNCTION: Heme-containing peroxygenase that mediates the hydroxylation
CC of 3-methyl-L-tyrosine (3-Me-Tyr) into 3-hydroxy-5-methyl-L-tyrosine
CC (3-OH-5-Me-Tyr) in biosynthesis of saframycin A, a potent antitumor
CC antibiotic that belongs to the tetrahydroisoquinoline family. Involved
CC in biosynthesis of 3-hydroxy-5-methyl-O-methyltyrosine (3-OH-5-Me-OMe-
CC Tyr), a core structure of saframycin A. {ECO:0000269|PubMed:19494690,
CC ECO:0000269|PubMed:22187429}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-methyl-L-tyrosine + H2O2 = 5-hydroxy-3-methyl-L-tyrosine +
CC H2O; Xref=Rhea:RHEA:41432, ChEBI:CHEBI:15377, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:78239, ChEBI:CHEBI:78241; EC=1.11.2.5;
CC Evidence={ECO:0000269|PubMed:22187429};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000269|PubMed:22187429};
CC Note=Binds 1 heme group per subunit. {ECO:0000269|PubMed:22187429};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.64 mM for 3-methyl-L-tyrosine {ECO:0000269|PubMed:22187429};
CC KM=1 mM for tyrosine {ECO:0000269|PubMed:22187429};
CC Note=kcat is 17.8 min(-1) with 3-methyl-L-tyrosine as substrate. kcat
CC is 12.3 min(-1) with L-tyrosine as substrate.
CC {ECO:0000269|PubMed:22187429};
CC pH dependence:
CC Optimum pH is 9.0. {ECO:0000269|PubMed:22187429};
CC -!- PATHWAY: Antibiotic biosynthesis. {ECO:0000269|PubMed:19494690,
CC ECO:0000269|PubMed:22187429}.
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DR EMBL; DQ838002; ABI22134.1; -; Genomic_DNA.
DR PDB; 6VDP; X-ray; 2.00 A; A=1-365.
DR PDB; 6VDQ; X-ray; 1.78 A; A=1-365.
DR PDB; 6VDZ; X-ray; 2.95 A; A=1-365.
DR PDB; 6VE0; X-ray; 3.15 A; A=1-365.
DR PDBsum; 6VDP; -.
DR PDBsum; 6VDQ; -.
DR PDBsum; 6VDZ; -.
DR PDBsum; 6VE0; -.
DR AlphaFoldDB; B0CN28; -.
DR SMR; B0CN28; -.
DR PRIDE; B0CN28; -.
DR KEGG; ag:ABI22134; -.
DR BioCyc; MetaCyc:MON-19337; -.
DR BRENDA; 1.11.2.5; 133.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR InterPro; IPR036271; Tet_transcr_reg_TetR-rel_C_sf.
DR SUPFAM; SSF48498; SSF48498; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic biosynthesis; Heme; Iron; Metal-binding;
KW Oxidoreductase.
FT CHAIN 1..365
FT /note="3-methyl-L-tyrosine peroxygenase"
FT /id="PRO_0000430695"
FT BINDING 313..317
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /evidence="ECO:0000269|PubMed:22187429"
FT MUTAGEN 191
FT /note="H->A: Does not affect heme-binding."
FT /evidence="ECO:0000269|PubMed:22187429"
FT MUTAGEN 274
FT /note="H->A: Does not affect heme-binding."
FT /evidence="ECO:0000269|PubMed:22187429"
FT MUTAGEN 313
FT /note="H->A: Almost abolishes heme-binding."
FT /evidence="ECO:0000269|PubMed:22187429"
FT MUTAGEN 317
FT /note="C->A: Almost abolishes heme-binding."
FT /evidence="ECO:0000269|PubMed:22187429"
FT TURN 18..20
FT /evidence="ECO:0007829|PDB:6VDQ"
FT STRAND 25..27
FT /evidence="ECO:0007829|PDB:6VDQ"
FT HELIX 30..32
FT /evidence="ECO:0007829|PDB:6VDQ"
FT HELIX 37..55
FT /evidence="ECO:0007829|PDB:6VDQ"
FT TURN 58..61
FT /evidence="ECO:0007829|PDB:6VDQ"
FT HELIX 64..77
FT /evidence="ECO:0007829|PDB:6VDQ"
FT HELIX 94..102
FT /evidence="ECO:0007829|PDB:6VDQ"
FT STRAND 105..108
FT /evidence="ECO:0007829|PDB:6VDQ"
FT HELIX 112..134
FT /evidence="ECO:0007829|PDB:6VDQ"
FT HELIX 140..158
FT /evidence="ECO:0007829|PDB:6VDQ"
FT HELIX 182..213
FT /evidence="ECO:0007829|PDB:6VDQ"
FT HELIX 217..251
FT /evidence="ECO:0007829|PDB:6VDQ"
FT HELIX 272..283
FT /evidence="ECO:0007829|PDB:6VDQ"
FT HELIX 285..293
FT /evidence="ECO:0007829|PDB:6VDQ"
FT HELIX 298..311
FT /evidence="ECO:0007829|PDB:6VDQ"
FT TURN 312..316
FT /evidence="ECO:0007829|PDB:6VDQ"
SQ SEQUENCE 365 AA; 38191 MW; 4EF655C3069E435C CRC64;
MTAPADTVHP AGQPDYVAQV ATVPFRLGRP EELPGTLDEL RAAVSARAGE AVRGLNRPGA
RTDLAALLAA TERTRAALAP VGAGPVGDDP SESEANRDND LAFGIVRTRG PVAELLVDAA
LAALAGILEV AVDRGSDLED AAWQRFIGGF DALLGWLADP HSAPRPATVP GAGPAGPPVH
QDALRRWVRG HHVFMVLAQG CALATACLRD SAARGDLPGA EASAAAAEAL MRGCQGALLY
AGDANREQYN EQIRPTLMPP VAPPKMSGLH WRDHEVLIKE LAGSRDAWEW LSAQGSERPA
TFRAALAETY DSHIGVCGHF VGDQSPSLLA AQGSTRSAVG VIGQFRKIRL SALPEQPATQ
QGEPS
