DNRK_STRS5
ID DNRK_STRS5 Reviewed; 356 AA.
AC Q55216;
DT 19-MAR-2014, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 73.
DE RecName: Full=Carminomycin 4-O-methyltransferase DauK;
DE Short=COMT;
DE EC=2.1.1.292;
DE AltName: Full=Anthracycline 4-O-methyltransferase;
GN Name=dauK;
OS Streptomyces sp. (strain C5).
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=45212;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=C5;
RX PubMed=7836284; DOI=10.1128/jb.177.3.536-543.1995;
RA Dickens M.L., Ye J., Strohl W.R.;
RT "Analysis of clustered genes encoding both early and late steps in
RT daunomycin biosynthesis by Streptomyces sp. strain C5.";
RL J. Bacteriol. 177:536-543(1995).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE
RP SPECIFICITY, ACTIVITY REGULATION, AND SUBUNIT.
RC STRAIN=C5;
RX PubMed=8360627; DOI=10.1099/00221287-139-6-1353;
RA Connors N.C., Strohl W.R.;
RT "Partial purification and properties of carminomycin 4-O-methyltransferase
RT from Streptomyces sp. strain C5.";
RL J. Gen. Microbiol. 139:1353-1362(1993).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBSTRATE SPECIFICITY.
RC STRAIN=C5;
RX PubMed=9098063; DOI=10.1128/jb.179.8.2641-2650.1997;
RA Dickens M.L., Priestley N.D., Strohl W.R.;
RT "In vivo and in vitro bioconversion of epsilon-rhodomycinone glycoside to
RT doxorubicin: functions of DauP, DauK, and DoxA.";
RL J. Bacteriol. 179:2641-2650(1997).
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), 10-carboxy-13-deoxycarminomycin, 13-deoxy-
CC carminomycin and 13-dihydrocarminomycin at the 4-hydroxyl position.
CC {ECO:0000269|PubMed:7836284, ECO:0000269|PubMed:8360627,
CC ECO:0000269|PubMed:9098063}.
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:8360627, ECO:0000269|PubMed:9098063};
CC -!- ACTIVITY REGULATION: Strongly inhibited by S-adenosyl-L-homocysteine
CC and weakly by adenine and methionine. {ECO:0000269|PubMed:8360627}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.5 uM for carminomycin {ECO:0000269|PubMed:8360627};
CC KM=1 uM for 13-dihydrocarminomycin {ECO:0000269|PubMed:8360627};
CC KM=25 uM for S-adenosyl-L-methionine {ECO:0000269|PubMed:8360627};
CC pH dependence:
CC Optimum pH is 8 and the values at pH 7.5 and 7.0 result in 60% and
CC 80% decreases in activity, respectively. No pH values above pH 8.0.
CC {ECO:0000269|PubMed:8360627};
CC Temperature dependence:
CC Optimum temperature is 37 degrees Celsius with about 10% decrease in
CC activity at 30 and 45 degrees Celsius. {ECO:0000269|PubMed:8360627};
CC -!- PATHWAY: Antibiotic biosynthesis; daunorubicin biosynthesis.
CC -!- PATHWAY: Antibiotic biosynthesis; carminomycin biosynthesis.
CC -!- SUBUNIT: Homodimer and homotetramer in equilibrium.
CC {ECO:0000305|PubMed:8360627}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. Cation-independent O-methyltransferase family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; L35154; AAB16938.1; -; Genomic_DNA.
DR AlphaFoldDB; Q55216; -.
DR SMR; Q55216; -.
DR KEGG; ag:AAB16938; -.
DR BRENDA; 2.1.1.292; 1284.
DR UniPathway; UPA00054; -.
DR UniPathway; UPA01040; -.
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; IMP: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.
PE 1: Evidence at protein level;
KW Antibiotic biosynthesis; Methyltransferase; S-adenosyl-L-methionine;
KW Transferase.
FT CHAIN 1..356
FT /note="Carminomycin 4-O-methyltransferase DauK"
FT /id="PRO_0000425682"
FT BINDING 153
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 163
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 187
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 210
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 237..238
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 252
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 257
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 303
FT /ligand="substrate"
FT /evidence="ECO:0000250"
SQ SEQUENCE 356 AA; 38727 MW; 8735E049F402FF65 CRC64;
MTAEPTVAAR PQQIDALRTL IRLGSLHTPM VVRTAATLRL VDHILAGART VKALAARTDT
RPEALLRLIR HLVAIGLLEE DAPGEFAPTE VGKLLADDHP AAQRAWHDLT QAVARADISF
TRLPEAIRSG RPTYESVYGK PFYEDLAGRP DLRASFDSLL ACDQDVAFDA PAAAHDWTNV
RHVLDVGGGK GGFAAAIARR APHVSATVLE MAGTVDTARS YLRDAGLSDR VDVVEGDFFE
PLPRRADAII LSFVLLNWPD HDAVRILTRC AEALEPGGRI LIHERDDLHE NSFNEQFTEL
DLRMLVFLGG ALRTREKWDG LAASAGLVVE EVRQLPSPTI PYDLSLLVLA PASTGA
