DNRK_STRPE
ID DNRK_STRPE Reviewed; 356 AA.
AC Q06528;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 100.
DE RecName: Full=Carminomycin 4-O-methyltransferase DnrK;
DE Short=COMT;
DE EC=2.1.1.292;
DE AltName: Full=Anthracycline 4-O-methyltransferase;
GN Name=dnrK;
OS Streptomyces peucetius.
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=1950;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PROTEIN SEQUENCE OF 2-18.
RC STRAIN=ATCC 29050 / DSM 40754 / JCM 9920 / NBRC 100596 / NCIMB 10972;
RX PubMed=8509343; DOI=10.1128/jb.175.12.3900-3904.1993;
RA Madduri K., Torti F., Colombo A.L., Hutchinson C.R.;
RT "Cloning and sequencing of a gene encoding carminomycin 4-O-
RT methyltransferase from Streptomyces peucetius and its expression in
RT Escherichia coli.";
RL J. Bacteriol. 175:3900-3904(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 29050 / DSM 40754 / JCM 9920 / NBRC 100596 / NCIMB 10972;
RX PubMed=7601857; DOI=10.1128/jb.177.13.3879-3884.1995;
RA Madduri K., Hutchinson C.R.;
RT "Functional characterization and transcriptional analysis of a gene cluster
RT governing early and late steps in daunorubicin biosynthesis in Streptomyces
RT peucetius.";
RL J. Bacteriol. 177:3879-3884(1995).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 2-355 IN COMPLEX WITH
RP S-ADENOSYL-L-HOMOCYSTEINE AND ANTHRACYCLINE ANALOG, FUNCTION, CATALYTIC
RP ACTIVITY, SUBSTRATE SPECIFICITY, AND SUBUNIT.
RX PubMed=15273252; DOI=10.1074/jbc.m407081200;
RA Jansson A., Koskiniemi H., Mantsala P., Niemi J., Schneider G.;
RT "Crystal structure of a ternary complex of DnrK, a methyltransferase in
RT daunorubicin biosynthesis, with bound products.";
RL J. Biol. Chem. 279:41149-41156(2004).
CC -!- FUNCTION: Involved in the biosynthesis of the anthracyclines
CC carminomycin and daunorubicin (daunomycin) which are aromatic
CC polyketide antibiotics that exhibit high cytotoxicity and are widely
CC applied in the chemotherapy of a variety of cancers. In vivo, catalyzes
CC the transfer of a methyl group from S-adenosyl-L-methionine to the 4-O-
CC position of carminomycin to form daunorubicin. In vitro, it also
CC methylates the anthracyclines rhodomycin D (10-carbomethoxy-13-
CC deoxycarminomycin) and 13-deoxy-carminomycin at the 4-hydroxyl
CC position. It is quite specific with respect to the length of the
CC carbohydrate chain at the C7 position, but it can accept substrates
CC with bulky substituent at C10 position. {ECO:0000269|PubMed:15273252}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=carminomycin + S-adenosyl-L-methionine = daunorubicin + H(+) +
CC S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:38311, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:64677,
CC ChEBI:CHEBI:75730; EC=2.1.1.292;
CC Evidence={ECO:0000269|PubMed:15273252};
CC -!- PATHWAY: Antibiotic biosynthesis; daunorubicin biosynthesis.
CC -!- PATHWAY: Antibiotic biosynthesis; carminomycin biosynthesis.
CC -!- SUBUNIT: Homodimer and homotetramer in equilibrium.
CC {ECO:0000269|PubMed:15273252}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. Cation-independent O-methyltransferase family.
CC {ECO:0000255|PROSITE-ProRule:PRU01020}.
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DR EMBL; L13453; AAA26712.1; -; Genomic_DNA.
DR EMBL; L40425; AAA99001.1; -; Genomic_DNA.
DR PIR; A47128; A47128.
DR PDB; 1TW2; X-ray; 2.50 A; A/B=2-356.
DR PDB; 1TW3; X-ray; 2.35 A; A/B=2-356.
DR PDB; 4WXH; X-ray; 1.90 A; A/B=2-356.
DR PDB; 5EEG; X-ray; 2.25 A; A/B=1-356.
DR PDB; 5EEH; X-ray; 1.82 A; A/B/C=1-356.
DR PDB; 5JR3; X-ray; 1.84 A; A/B/C=10-353.
DR PDBsum; 1TW2; -.
DR PDBsum; 1TW3; -.
DR PDBsum; 4WXH; -.
DR PDBsum; 5EEG; -.
DR PDBsum; 5EEH; -.
DR PDBsum; 5JR3; -.
DR AlphaFoldDB; Q06528; -.
DR SMR; Q06528; -.
DR DrugBank; DB03199; 4-Methoxy-E-Rhodomycin T.
DR DrugBank; DB01752; S-adenosyl-L-homocysteine.
DR KEGG; ag:AAA26712; -.
DR BioCyc; MetaCyc:MON-18173; -.
DR BRENDA; 2.1.1.292; 6073.
DR UniPathway; UPA00054; -.
DR UniPathway; UPA01040; -.
DR EvolutionaryTrace; Q06528; -.
DR GO; GO:0008168; F:methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0008171; F:O-methyltransferase activity; IEA:InterPro.
DR GO; GO:1901771; P:daunorubicin biosynthetic process; IDA:UniProtKB.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR016461; COMT-like.
DR InterPro; IPR001077; O_MeTrfase_dom.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00891; Methyltransf_2; 1.
DR PIRSF; PIRSF005739; O-mtase; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51683; SAM_OMT_II; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic biosynthesis; Direct protein sequencing;
KW Methyltransferase; S-adenosyl-L-methionine; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:8509343"
FT CHAIN 2..356
FT /note="Carminomycin 4-O-methyltransferase DnrK"
FT /id="PRO_0000089881"
FT BINDING 153
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 163
FT /ligand="substrate"
FT BINDING 187
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 210
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 237..238
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 252
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 257
FT /ligand="substrate"
FT BINDING 303
FT /ligand="substrate"
FT HELIX 14..24
FT /evidence="ECO:0007829|PDB:5EEH"
FT HELIX 27..37
FT /evidence="ECO:0007829|PDB:5EEH"
FT HELIX 40..45
FT /evidence="ECO:0007829|PDB:5EEH"
FT HELIX 51..58
FT /evidence="ECO:0007829|PDB:5EEH"
FT HELIX 62..74
FT /evidence="ECO:0007829|PDB:5EEH"
FT STRAND 77..82
FT /evidence="ECO:0007829|PDB:5EEH"
FT STRAND 85..88
FT /evidence="ECO:0007829|PDB:5EEH"
FT HELIX 92..95
FT /evidence="ECO:0007829|PDB:5EEH"
FT HELIX 103..106
FT /evidence="ECO:0007829|PDB:5EEH"
FT HELIX 112..116
FT /evidence="ECO:0007829|PDB:5EEH"
FT HELIX 117..122
FT /evidence="ECO:0007829|PDB:5EEH"
FT HELIX 123..129
FT /evidence="ECO:0007829|PDB:5EEH"
FT HELIX 134..138
FT /evidence="ECO:0007829|PDB:5EEH"
FT HELIX 142..148
FT /evidence="ECO:0007829|PDB:5EEH"
FT HELIX 150..160
FT /evidence="ECO:0007829|PDB:5EEH"
FT TURN 161..163
FT /evidence="ECO:0007829|PDB:4WXH"
FT HELIX 164..167
FT /evidence="ECO:0007829|PDB:5EEH"
FT HELIX 169..173
FT /evidence="ECO:0007829|PDB:5EEH"
FT STRAND 181..186
FT /evidence="ECO:0007829|PDB:5EEH"
FT HELIX 192..200
FT /evidence="ECO:0007829|PDB:5EEH"
FT STRAND 205..210
FT /evidence="ECO:0007829|PDB:5EEH"
FT HELIX 214..224
FT /evidence="ECO:0007829|PDB:5EEH"
FT TURN 228..230
FT /evidence="ECO:0007829|PDB:5EEH"
FT STRAND 231..235
FT /evidence="ECO:0007829|PDB:5EEH"
FT STRAND 246..253
FT /evidence="ECO:0007829|PDB:5EEH"
FT HELIX 255..257
FT /evidence="ECO:0007829|PDB:5EEH"
FT HELIX 260..272
FT /evidence="ECO:0007829|PDB:5EEH"
FT STRAND 274..284
FT /evidence="ECO:0007829|PDB:5EEH"
FT HELIX 289..291
FT /evidence="ECO:0007829|PDB:5EEH"
FT HELIX 295..308
FT /evidence="ECO:0007829|PDB:5EEH"
FT HELIX 315..324
FT /evidence="ECO:0007829|PDB:5EEH"
FT STRAND 327..334
FT /evidence="ECO:0007829|PDB:5EEH"
FT STRAND 338..340
FT /evidence="ECO:0007829|PDB:5EEH"
FT STRAND 345..351
FT /evidence="ECO:0007829|PDB:5EEH"
SQ SEQUENCE 356 AA; 38782 MW; 2969EC5C6117ECF7 CRC64;
MTAEPTVAAR PQQIDALRTL IRLGSLHTPM VVRTAATLRL VDHILAGART VKALAARTDT
RPEALLRLIR HLVAIGLLEE DAPGEFVPTE VGELLADDHP AAQRAWHDLT QAVARADISF
TRLPDAIRTG RPTYESIYGK PFYEDLAGRP DLRASFDSLL ACDQDVAFDA PAAAYDWTNV
RHVLDVGGGK GGFAAAIARR APHVSATVLE MAGTVDTARS YLKDEGLSDR VDVVEGDFFE
PLPRKADAII LSFVLLNWPD HDAVRILTRC AEALEPGGRI LIHERDDLHE NSFNEQFTEL
DLRMLVFLGG ALRTREKWDG LAASAGLVVE EVRQLPSPTI PYDLSLLVLA PAATGA
