RDMB_STREF
ID RDMB_STREF Reviewed; 374 AA.
AC Q54527;
DT 19-MAR-2014, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Aclacinomycin 10-hydroxylase RdmB;
DE EC=4.1.1.-;
DE AltName: Full=15-demethoxy-epsilon-rhodomycin 10-hydroxylase;
DE AltName: Full=15-demethoxyaclacinomycin T;
GN Name=rdmB;
OS Streptomyces purpurascens.
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=1924;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 25489 / DSM 40310 / JCM 4509 / NBRC 13077 / Maria 515;
RX PubMed=8081500; DOI=10.1099/00221287-140-6-1351;
RA Niemi J., Ylihonko K., Hakala J., Parssinen R., Kopio A., Mantsala P.;
RT "Hybrid anthracycline antibiotics: production of new anthracyclines by
RT cloned genes from Streptomyces purpurascens in Streptomyces galilaeus.";
RL Microbiology 140:1351-1358(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 25489 / DSM 40310 / JCM 4509 / NBRC 13077 / Maria 515;
RX PubMed=7751313; DOI=10.1128/jb.177.10.2942-2945.1995;
RA Niemi J., Mantsala P.;
RT "Nucleotide sequences and expression of genes from Streptomyces
RT purpurascens that cause the production of new anthracyclines in
RT Streptomyces galilaeus.";
RL J. Bacteriol. 177:2942-2945(1995).
RN [3]
RP PROTEIN SEQUENCE OF 1-8, FUNCTION, CATALYTIC ACTIVITY, AND SUBUNIT.
RC STRAIN=ATCC 25489 / DSM 40310 / JCM 4509 / NBRC 13077 / Maria 515;
RX PubMed=11004563; DOI=10.1016/s0167-4838(00)00089-3;
RA Wang Y., Niemi J., Airas K., Ylihonko K., Hakala J., Mantsala P.;
RT "Modifications of aclacinomycin T by aclacinomycin methyl esterase (RdmC)
RT and aclacinomycin-10-hydroxylase (RdmB) from Streptomyces purpurascens.";
RL Biochim. Biophys. Acta 1480:191-200(2000).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH
RP S-ADENOSYL-L-METHIONINE, AND SUBUNIT.
RX PubMed=14607118; DOI=10.1016/j.jmb.2003.09.061;
RA Jansson A., Niemi J., Lindqvist Y., Mantsala P., Schneider G.;
RT "Crystal structure of aclacinomycin-10-hydroxylase, a S-adenosyl-L-
RT methionine-dependent methyltransferase homolog involved in anthracycline
RT biosynthesis in Streptomyces purpurascens.";
RL J. Mol. Biol. 334:269-280(2003).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH
RP S-ADENOSYL-L-METHIONINE AND SUBSTRATE, FUNCTION, CATALYTIC ACTIVITY,
RP MUTAGENESIS OF CYS-165, ACTIVITY REGULATION, REACTION MECHANISM, AND
RP SUBUNIT.
RX PubMed=15548527; DOI=10.1074/jbc.m412095200;
RA Jansson A., Koskiniemi H., Erola A., Wang J., Mantsala P., Schneider G.,
RA Niemi J.;
RT "Aclacinomycin 10-hydroxylase is a novel substrate-assisted hydroxylase
RT requiring S-adenosyl-L-methionine as cofactor.";
RL J. Biol. Chem. 280:3636-3644(2005).
CC -!- FUNCTION: Involved in the biosynthesis of the anthracycline
CC aclacinomycin which is an aromatic polyketide antibiotic that exhibits
CC high cytotoxicity and is widely applied in the chemotherapy of a
CC variety of cancers. In vivo and in vitro, RdmB catalyzes the removal of
CC the carboxylic group from the C-10 position of 15-
CC demethoxyaclacinomycin T coupled to hydroxylation at the same C-10
CC position. It could also catalyze the removal of the carboxylic group at
CC the C-10 position of 15-demethoxy-epsilon-rhodomycin coupled to
CC hydroxylation at the same C-10 position to yield rhodomycin B. The
CC reaction catalyzes by RdmB is intriguing, since the enzyme does not use
CC any of the cofactors usually associated with hydroxylases such as
CC flavins and/or metal ions to activate molecular oxygen.
CC {ECO:0000269|PubMed:11004563, ECO:0000269|PubMed:15548527}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=15-demethylaclacinomycin T + AH2 + O2 = 10-
CC decarboxymethylaclacinomycin T + A + CO2 + H2O; Xref=Rhea:RHEA:45800,
CC ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:17499, ChEBI:CHEBI:74354,
CC ChEBI:CHEBI:85430; Evidence={ECO:0000269|PubMed:11004563,
CC ECO:0000269|PubMed:15548527};
CC -!- ACTIVITY REGULATION: Inhibited by sinefungin and S-adenosyl-L-
CC homocysteine. {ECO:0000269|PubMed:15548527}.
CC -!- PATHWAY: Antibiotic biosynthesis; aclacinomycin biosynthesis.
CC -!- PATHWAY: Antibiotic biosynthesis; rhodomycin biosynthesis.
CC -!- SUBUNIT: Homodimer and homotetramer in equilibrium.
CC {ECO:0000269|PubMed:11004563, ECO:0000269|PubMed:14607118,
CC ECO:0000269|PubMed:15548527}.
CC -!- MISCELLANEOUS: Although RdmB shows significant similarity to
CC methyltransferase family, it cannot act as a methyltransferase.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. Cation-independent O-methyltransferase family.
CC {ECO:0000305}.
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DR EMBL; U10405; AAA83421.1; -; Genomic_DNA.
DR PDB; 1QZZ; X-ray; 2.10 A; A=1-374.
DR PDB; 1R00; X-ray; 2.50 A; A=1-374.
DR PDB; 1XDS; X-ray; 2.30 A; A/B=1-374.
DR PDB; 1XDU; X-ray; 2.70 A; A=1-374.
DR PDBsum; 1QZZ; -.
DR PDBsum; 1R00; -.
DR PDBsum; 1XDS; -.
DR PDBsum; 1XDU; -.
DR AlphaFoldDB; Q54527; -.
DR SMR; Q54527; -.
DR DrugBank; DB03219; 11-Deoxy-Beta-Rhodomycin.
DR DrugBank; DB01752; S-adenosyl-L-homocysteine.
DR DrugBank; DB01910; Sinefungin.
DR KEGG; ag:AAA83421; -.
DR BioCyc; MetaCyc:MON-18185; -.
DR UniPathway; UPA01042; -.
DR UniPathway; UPA01043; -.
DR EvolutionaryTrace; Q54527; -.
DR GO; GO:0016831; F:carboxy-lyase activity; IDA:UniProtKB.
DR GO; GO:0008171; F:O-methyltransferase activity; IEA:InterPro.
DR GO; GO:0017000; P:antibiotic biosynthetic process; 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; Lyase;
KW S-adenosyl-L-methionine.
FT CHAIN 1..374
FT /note="Aclacinomycin 10-hydroxylase RdmB"
FT /id="PRO_0000425720"
FT BINDING 171
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:14607118,
FT ECO:0000269|PubMed:15548527"
FT BINDING 190
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:14607118,
FT ECO:0000269|PubMed:15548527"
FT BINDING 213
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:14607118,
FT ECO:0000269|PubMed:15548527"
FT BINDING 240..241
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 255
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:14607118,
FT ECO:0000269|PubMed:15548527"
FT BINDING 260
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:15548527"
FT MUTAGEN 165
FT /note="C->S: Approximately equally active as the native
FT enzyme."
FT /evidence="ECO:0000269|PubMed:15548527"
FT HELIX 14..22
FT /evidence="ECO:0007829|PDB:1QZZ"
FT TURN 23..25
FT /evidence="ECO:0007829|PDB:1QZZ"
FT HELIX 28..38
FT /evidence="ECO:0007829|PDB:1QZZ"
FT HELIX 41..46
FT /evidence="ECO:0007829|PDB:1QZZ"
FT HELIX 52..59
FT /evidence="ECO:0007829|PDB:1QZZ"
FT HELIX 63..75
FT /evidence="ECO:0007829|PDB:1QZZ"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:1QZZ"
FT HELIX 95..98
FT /evidence="ECO:0007829|PDB:1QZZ"
FT HELIX 106..110
FT /evidence="ECO:0007829|PDB:1QZZ"
FT HELIX 115..120
FT /evidence="ECO:0007829|PDB:1QZZ"
FT HELIX 121..125
FT /evidence="ECO:0007829|PDB:1QZZ"
FT HELIX 126..132
FT /evidence="ECO:0007829|PDB:1QZZ"
FT HELIX 137..141
FT /evidence="ECO:0007829|PDB:1QZZ"
FT HELIX 145..151
FT /evidence="ECO:0007829|PDB:1QZZ"
FT HELIX 153..161
FT /evidence="ECO:0007829|PDB:1QZZ"
FT HELIX 164..166
FT /evidence="ECO:0007829|PDB:1QZZ"
FT TURN 168..171
FT /evidence="ECO:0007829|PDB:1QZZ"
FT HELIX 172..176
FT /evidence="ECO:0007829|PDB:1QZZ"
FT STRAND 185..189
FT /evidence="ECO:0007829|PDB:1QZZ"
FT HELIX 195..203
FT /evidence="ECO:0007829|PDB:1QZZ"
FT STRAND 208..213
FT /evidence="ECO:0007829|PDB:1QZZ"
FT HELIX 215..227
FT /evidence="ECO:0007829|PDB:1QZZ"
FT TURN 231..233
FT /evidence="ECO:0007829|PDB:1QZZ"
FT STRAND 234..238
FT /evidence="ECO:0007829|PDB:1QZZ"
FT STRAND 249..256
FT /evidence="ECO:0007829|PDB:1QZZ"
FT HELIX 258..260
FT /evidence="ECO:0007829|PDB:1QZZ"
FT HELIX 263..276
FT /evidence="ECO:0007829|PDB:1QZZ"
FT STRAND 277..287
FT /evidence="ECO:0007829|PDB:1QZZ"
FT HELIX 297..312
FT /evidence="ECO:0007829|PDB:1QZZ"
FT HELIX 319..327
FT /evidence="ECO:0007829|PDB:1QZZ"
FT TURN 328..330
FT /evidence="ECO:0007829|PDB:1QZZ"
FT STRAND 331..339
FT /evidence="ECO:0007829|PDB:1QZZ"
FT STRAND 342..345
FT /evidence="ECO:0007829|PDB:1XDS"
FT STRAND 348..355
FT /evidence="ECO:0007829|PDB:1QZZ"
SQ SEQUENCE 374 AA; 39797 MW; 427F37F5C59EEAD2 CRC64;
MSSSSPGEPL EPTDQDLDVL LKNLGNLVTP MALRVAATLR LVDHLLAGAD TLAGLADRTD
THPQALSRLV RHLTVVGVLE GGEKQGRPLR PTRLGMLLAD GHPAQQRAWL DLNGAVSHAD
LAFTGLLDVV RTGRPAYAGR YGRPFWEDLS ADVALADSFD ALMSCDEDLA YEAPADAYDW
SAVRHVLDVG GGNGGMLAAI ALRAPHLRGT LVELAGPAER ARRRFADAGL ADRVTVAEGD
FFKPLPVTAD VVLLSFVLLN WSDEDALTIL RGCVRALEPG GRLLVLDRAD VEGDGADRFF
STLLDLRMLT FMGGRVRTRD EVVDLAGSAG LALASERTSG STTLPFDFSI LEFTAVSEEA
APAAQASEAL PAQE
