C167_SORCE
ID C167_SORCE Reviewed; 419 AA.
AC Q9KIZ4; Q9L8C4;
DT 02-FEB-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 86.
DE RecName: Full=Epothilone C/D epoxidase {ECO:0000303|PubMed:10831849};
DE EC=1.14.15.- {ECO:0000269|PubMed:10831849};
DE AltName: Full=Cytochrome P450 167A1;
DE AltName: Full=Cytochrome P450epoK {ECO:0000303|PubMed:12933799};
GN Name=cyp167A1; Synonyms=epoF, epoK;
OS Sorangium cellulosum (Polyangium cellulosum).
OC Bacteria; Proteobacteria; Deltaproteobacteria; Myxococcales; Sorangiineae;
OC Polyangiaceae; Sorangium.
OX NCBI_TaxID=56 {ECO:0000312|EMBL:AAF62886.1};
RN [1] {ECO:0000312|EMBL:AAF26924.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=So ce90;
RX PubMed=10662695; DOI=10.1016/s1074-5521(00)00075-2;
RA Molnar I., Schupp T., Ono M., Zirkle R.E., Milnamow M., Nowak-Thompson B.,
RA Engel N., Toupet C., Stratmann A., Cyr D.D., Gorlach J., Mayo J.M., Hu A.,
RA Goff S., Schmid J., Ligon J.M.;
RT "The biosynthetic gene cluster for the microtubule-stabilizing agents
RT epothilones A and B from Sorangium cellulosum So ce90.";
RL Chem. Biol. 7:97-109(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP PATHWAY.
RC STRAIN=SMP44 {ECO:0000312|EMBL:AAF62886.1};
RX PubMed=10831849; DOI=10.1016/s0378-1119(00)00149-9;
RA Julien B., Shah S., Ziermann R., Goldman R., Katz L., Khosla C.;
RT "Isolation and characterization of the epothilone biosynthetic gene cluster
RT from Sorangium cellulosum.";
RL Gene 249:153-160(2000).
RN [3] {ECO:0000312|EMBL:AAF62886.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=SMP44 {ECO:0000312|EMBL:AAF62886.1};
RX PubMed=10649995; DOI=10.1126/science.287.5453.640;
RA Tang L., Shah S., Chung L., Carney J., Katz L., Khosla C., Julien B.;
RT "Cloning and heterologous expression of the epothilone gene cluster.";
RL Science 287:640-642(2000).
RN [4] {ECO:0000305}
RP X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) IN COMPLEXES WITH HEME; EPOTHILONE D
RP AND EPOTHILONE B, AND COFACTOR.
RX PubMed=12933799; DOI=10.1074/jbc.m308115200;
RA Nagano S., Li H., Shimizu H., Nishida C., Ogura H.,
RA Ortiz De Montellano P.R., Poulos T.L.;
RT "Crystal structures of epothilone D-bound, epothilone B-bound, and
RT substrate-free forms of cytochrome P450epoK.";
RL J. Biol. Chem. 278:44886-44893(2003).
CC -!- FUNCTION: Involved in the biosynthesis of epothilones, macrolactones
CC which have a narrow anti-fungal spectrum and microtubule-stabilizing
CC activity. Catalyzes the epoxidation of epothilones C and D to
CC epothilones A and B, respectively. {ECO:0000269|PubMed:10831849}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=epothilone C + 2 H(+) + O2 + 2 reduced [2Fe-2S]-[ferredoxin] =
CC epothilone A + H2O + 2 oxidized [2Fe-2S]-[ferredoxin];
CC Xref=Rhea:RHEA:47804, Rhea:RHEA-COMP:10000, Rhea:RHEA-COMP:10001,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:31549, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738,
CC ChEBI:CHEBI:80029; Evidence={ECO:0000269|PubMed:10831849};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=epothilone D + 2 H(+) + O2 + 2 reduced [2Fe-2S]-[ferredoxin] =
CC epothilone B + H2O + 2 oxidized [2Fe-2S]-[ferredoxin];
CC Xref=Rhea:RHEA:47808, Rhea:RHEA-COMP:10000, Rhea:RHEA-COMP:10001,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:29579, ChEBI:CHEBI:31550, ChEBI:CHEBI:33737,
CC ChEBI:CHEBI:33738; Evidence={ECO:0000269|PubMed:10831849};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000269|PubMed:12933799};
CC -!- PATHWAY: Secondary metabolite biosynthesis; epothilone biosynthesis.
CC {ECO:0000269|PubMed:10831849}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family.
CC {ECO:0000255|RuleBase:RU000461, ECO:0000305}.
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DR EMBL; AF210843; AAF26924.1; -; Genomic_DNA.
DR EMBL; AF217189; AAF62886.1; -; Genomic_DNA.
DR PDB; 1PKF; X-ray; 2.10 A; A=1-419.
DR PDB; 1Q5D; X-ray; 1.93 A; A=1-419.
DR PDB; 1Q5E; X-ray; 2.65 A; A=1-419.
DR PDBsum; 1PKF; -.
DR PDBsum; 1Q5D; -.
DR PDBsum; 1Q5E; -.
DR AlphaFoldDB; Q9KIZ4; -.
DR SMR; Q9KIZ4; -.
DR PRIDE; Q9KIZ4; -.
DR KEGG; ag:AAF62886; -.
DR UniPathway; UPA00774; -.
DR EvolutionaryTrace; Q9KIZ4; -.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; NAS:UniProtKB.
DR GO; GO:0050814; P:epothilone biosynthetic process; IDA:UniProtKB.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR002397; Cyt_P450_B.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00359; BP450.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase.
FT CHAIN 1..419
FT /note="Epothilone C/D epoxidase"
FT /id="PRO_0000052241"
FT BINDING 180
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:12933799"
FT BINDING 304
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:12933799"
FT BINDING 365
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000269|PubMed:12933799"
FT CONFLICT 190
FT /note="R -> Q (in Ref. 1; AAF26924)"
FT /evidence="ECO:0000305"
FT CONFLICT 211
FT /note="G -> D (in Ref. 1; AAF26924)"
FT /evidence="ECO:0000305"
FT CONFLICT 353
FT /note="S -> G (in Ref. 1; AAF26924)"
FT /evidence="ECO:0000305"
FT TURN 22..26
FT /evidence="ECO:0007829|PDB:1Q5D"
FT HELIX 29..38
FT /evidence="ECO:0007829|PDB:1Q5D"
FT STRAND 40..44
FT /evidence="ECO:0007829|PDB:1Q5D"
FT TURN 45..48
FT /evidence="ECO:0007829|PDB:1Q5D"
FT STRAND 49..52
FT /evidence="ECO:0007829|PDB:1Q5D"
FT HELIX 55..62
FT /evidence="ECO:0007829|PDB:1Q5D"
FT HELIX 71..73
FT /evidence="ECO:0007829|PDB:1Q5D"
FT HELIX 77..82
FT /evidence="ECO:0007829|PDB:1Q5D"
FT HELIX 85..87
FT /evidence="ECO:0007829|PDB:1Q5D"
FT HELIX 88..93
FT /evidence="ECO:0007829|PDB:1Q5D"
FT TURN 95..97
FT /evidence="ECO:0007829|PDB:1Q5D"
FT HELIX 100..110
FT /evidence="ECO:0007829|PDB:1Q5D"
FT HELIX 111..114
FT /evidence="ECO:0007829|PDB:1Q5D"
FT HELIX 116..119
FT /evidence="ECO:0007829|PDB:1Q5D"
FT HELIX 120..122
FT /evidence="ECO:0007829|PDB:1Q5D"
FT HELIX 123..137
FT /evidence="ECO:0007829|PDB:1Q5D"
FT TURN 145..149
FT /evidence="ECO:0007829|PDB:1Q5D"
FT HELIX 150..152
FT /evidence="ECO:0007829|PDB:1Q5D"
FT HELIX 154..161
FT /evidence="ECO:0007829|PDB:1Q5D"
FT HELIX 166..168
FT /evidence="ECO:0007829|PDB:1Q5D"
FT HELIX 169..182
FT /evidence="ECO:0007829|PDB:1Q5D"
FT TURN 183..187
FT /evidence="ECO:0007829|PDB:1Q5D"
FT HELIX 195..218
FT /evidence="ECO:0007829|PDB:1Q5D"
FT HELIX 225..234
FT /evidence="ECO:0007829|PDB:1Q5D"
FT STRAND 235..238
FT /evidence="ECO:0007829|PDB:1PKF"
FT HELIX 241..255
FT /evidence="ECO:0007829|PDB:1Q5D"
FT HELIX 257..272
FT /evidence="ECO:0007829|PDB:1Q5D"
FT HELIX 274..282
FT /evidence="ECO:0007829|PDB:1Q5D"
FT HELIX 284..286
FT /evidence="ECO:0007829|PDB:1Q5D"
FT HELIX 287..297
FT /evidence="ECO:0007829|PDB:1Q5D"
FT STRAND 300..311
FT /evidence="ECO:0007829|PDB:1Q5D"
FT STRAND 313..315
FT /evidence="ECO:0007829|PDB:1Q5D"
FT STRAND 318..320
FT /evidence="ECO:0007829|PDB:1Q5D"
FT STRAND 325..329
FT /evidence="ECO:0007829|PDB:1Q5D"
FT HELIX 330..333
FT /evidence="ECO:0007829|PDB:1Q5D"
FT TURN 337..339
FT /evidence="ECO:0007829|PDB:1Q5D"
FT STRAND 340..342
FT /evidence="ECO:0007829|PDB:1Q5D"
FT HELIX 361..363
FT /evidence="ECO:0007829|PDB:1Q5D"
FT HELIX 368..385
FT /evidence="ECO:0007829|PDB:1Q5D"
FT STRAND 401..403
FT /evidence="ECO:0007829|PDB:1Q5D"
FT STRAND 406..408
FT /evidence="ECO:0007829|PDB:1Q5D"
FT STRAND 410..414
FT /evidence="ECO:0007829|PDB:1Q5D"
SQ SEQUENCE 419 AA; 46750 MW; FCCE0A193563688F CRC64;
MTQEQANQSE TKPAFDFKPF APGYAEDPFP AIERLREATP IFYWDEGRSW VLTRYHDVSA
VFRDERFAVS REEWESSAEY SSAIPELSDM KKYGLFGLPP EDHARVRKLV NPSFTSRAID
LLRAEIQRTV DQLLDARSGQ EEFDVVRDYA EGIPMRAISA LLKVPAECDE KFRRFGSATA
RALGVGLVPR VDEETKTLVA SVTEGLALLH GVLDERRRNP LENDVLTMLL QAEADGSRLS
TKELVALVGA IIAAGTDTTI YLIAFAVLNL LRSPEALELV KAEPGLMRNA LDEVLRFDNI
LRIGTVRFAR QDLEYCGASI KKGEMVFLLI PSALRDGTVF SRPDVFDVRR DTSASLAYGR
GPHVCPGVSL ARLEAEIAVG TIFRRFPEMK LKETPVFGYH PAFRNIESLN VILKPSKAG
