C1582_STRCO
ID C1582_STRCO Reviewed; 404 AA.
AC Q9FCA6;
DT 29-OCT-2014, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Biflaviolin synthase CYP158A2;
DE EC=1.14.19.69 {ECO:0000269|PubMed:15659395, ECO:0000269|PubMed:16239228, ECO:0000269|PubMed:22203090};
DE AltName: Full=Cytochrome P450 158A2 {ECO:0000303|PubMed:15659395};
DE Short=CYP158A2 {ECO:0000303|PubMed:15659395};
GN Name=cyp158a2 {ECO:0000303|PubMed:15659395};
GN OrderedLocusNames=SCO1207 {ECO:0000312|EMBL:CAC01489.1};
OS Streptomyces coelicolor (strain ATCC BAA-471 / A3(2) / M145).
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces; Streptomyces albidoflavus group.
OX NCBI_TaxID=100226;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC BAA-471 / A3(2) / M145;
RX PubMed=12000953; DOI=10.1038/417141a;
RA Bentley S.D., Chater K.F., Cerdeno-Tarraga A.-M., Challis G.L.,
RA Thomson N.R., James K.D., Harris D.E., Quail M.A., Kieser H., Harper D.,
RA Bateman A., Brown S., Chandra G., Chen C.W., Collins M., Cronin A.,
RA Fraser A., Goble A., Hidalgo J., Hornsby T., Howarth S., Huang C.-H.,
RA Kieser T., Larke L., Murphy L.D., Oliver K., O'Neil S., Rabbinowitsch E.,
RA Rajandream M.A., Rutherford K.M., Rutter S., Seeger K., Saunders D.,
RA Sharp S., Squares R., Squares S., Taylor K., Warren T., Wietzorrek A.,
RA Woodward J.R., Barrell B.G., Parkhill J., Hopwood D.A.;
RT "Complete genome sequence of the model actinomycete Streptomyces coelicolor
RT A3(2).";
RL Nature 417:141-147(2002).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) IN COMPLEX WITH HEME AND SUBSTRATE,
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=15659395; DOI=10.1074/jbc.m410933200;
RA Zhao B., Guengerich F.P., Bellamine A., Lamb D.C., Izumikawa M., Lei L.,
RA Podust L.M., Sundaramoorthy M., Kalaitzis J.A., Reddy L.M., Kelly S.L.,
RA Moore B.S., Stec D., Voehler M., Falck J.R., Shimada T., Waterman M.R.;
RT "Binding of two flaviolin substrate molecules, oxidative coupling, and
RT crystal structure of Streptomyces coelicolor A3(2) cytochrome P450 158A2.";
RL J. Biol. Chem. 280:11599-11607(2005).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH HEME AND SUBSTRATE,
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND PROTON
RP WIRE.
RX PubMed=16239228; DOI=10.1074/jbc.m509220200;
RA Zhao B., Guengerich F.P., Voehler M., Waterman M.R.;
RT "Role of active site water molecules and substrate hydroxyl groups in
RT oxygen activation by cytochrome P450 158A2: a new mechanism of proton
RT transfer.";
RL J. Biol. Chem. 280:42188-42197(2005).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.76 ANGSTROMS) IN COMPLEX WITH HEME, MUTAGENESIS OF
RP ILE-87, BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY, AND
RP REGIOSPECIFICITY SITE.
RX PubMed=22203090; DOI=10.1016/j.abb.2011.12.007;
RA Zhao B., Bellamine A., Lei L., Waterman M.R.;
RT "The role of Ile87 of CYP158A2 in oxidative coupling reaction.";
RL Arch. Biochem. Biophys. 518:127-132(2012).
CC -!- FUNCTION: Catalyzes oxidative C-C coupling reaction to polymerize
CC flaviolin and form highly conjugated pigments which protect the soil
CC bacterium from deleterious effects of UV irradiation (three isomers of
CC biflaviolin and one triflaviolin). {ECO:0000269|PubMed:15659395,
CC ECO:0000269|PubMed:16239228}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 flaviolin + H(+) + O2 + 2 reduced [2Fe-2S]-[ferredoxin] =
CC 3,3'-biflaviolin + 2 H2O + 2 oxidized [2Fe-2S]-[ferredoxin];
CC Xref=Rhea:RHEA:26031, Rhea:RHEA-COMP:10000, Rhea:RHEA-COMP:10001,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:58696,
CC ChEBI:CHEBI:77877; EC=1.14.19.69;
CC Evidence={ECO:0000269|PubMed:15659395, ECO:0000269|PubMed:16239228,
CC ECO:0000269|PubMed:22203090};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 flaviolin + H(+) + O2 + 2 reduced [2Fe-2S]-[ferredoxin] =
CC 3,8'-biflaviolin + 2 H2O + 2 oxidized [2Fe-2S]-[ferredoxin];
CC Xref=Rhea:RHEA:26035, Rhea:RHEA-COMP:10000, Rhea:RHEA-COMP:10001,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:58696,
CC ChEBI:CHEBI:77840; EC=1.14.19.69;
CC Evidence={ECO:0000269|PubMed:15659395, ECO:0000269|PubMed:16239228,
CC ECO:0000269|PubMed:22203090};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000269|PubMed:15659395, ECO:0000269|PubMed:16239228,
CC ECO:0000269|PubMed:22203090};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=7.3 uM for flaviolin (at pH 8.2 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:22203090};
CC Note=kcat is 1.4 min(-1) with flaviolin as substrate (at pH 7.5 and
CC 37 degrees Celsius). kcat is 0.02 min(-1) with 2-hydroxy-1,4-
CC naphthoquinone as substrate (at pH 7.5 and 25 degrees Celsius).
CC {ECO:0000269|PubMed:15659395, ECO:0000269|PubMed:16239228};
CC -!- PATHWAY: Pigment biosynthesis. {ECO:0000303|PubMed:15659395}.
CC -!- MISCELLANEOUS: The structural studies suggest catalysis likely occurs
CC through proton relay via a 'proton wire' formed by water molecules in
CC the active site. {ECO:0000269|PubMed:16239228,
CC ECO:0000269|PubMed:22203090}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family.
CC {ECO:0000255|RuleBase:RU000461}.
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DR EMBL; AL939108; CAC01489.1; -; Genomic_DNA.
DR RefSeq; NP_625496.1; NC_003888.3.
DR RefSeq; WP_003977624.1; NZ_VNID01000006.1.
DR PDB; 1S1F; X-ray; 1.50 A; A=1-404.
DR PDB; 1SE6; X-ray; 1.75 A; A/B=1-404.
DR PDB; 1T93; X-ray; 1.62 A; A=1-404.
DR PDB; 2D09; X-ray; 1.80 A; A=1-404.
DR PDB; 2D0E; X-ray; 2.15 A; A=1-404.
DR PDB; 3TZO; X-ray; 1.76 A; A/B=1-404.
DR PDB; 5DE9; X-ray; 1.76 A; A/B=1-404.
DR PDBsum; 1S1F; -.
DR PDBsum; 1SE6; -.
DR PDBsum; 1T93; -.
DR PDBsum; 2D09; -.
DR PDBsum; 2D0E; -.
DR PDBsum; 3TZO; -.
DR PDBsum; 5DE9; -.
DR AlphaFoldDB; Q9FCA6; -.
DR SMR; Q9FCA6; -.
DR STRING; 100226.SCO1207; -.
DR DrugBank; DB03814; 2-(N-morpholino)ethanesulfonic acid.
DR DrugBank; DB03254; 4-Phenyl-1h-Imidazole.
DR DrugBank; DB02521; Flaviolin.
DR DrugBank; DB02175; Malonic acid.
DR GeneID; 1096630; -.
DR KEGG; sco:SCO1207; -.
DR PATRIC; fig|100226.15.peg.1206; -.
DR eggNOG; COG2124; Bacteria.
DR HOGENOM; CLU_033716_1_1_11; -.
DR InParanoid; Q9FCA6; -.
DR OMA; IPHRNAV; -.
DR PhylomeDB; Q9FCA6; -.
DR BioCyc; MetaCyc:MON-14458; -.
DR BRENDA; 1.14.19.69; 5998.
DR EvolutionaryTrace; Q9FCA6; -.
DR Proteomes; UP000001973; Chromosome.
DR GO; GO:0020037; F:heme binding; IDA:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IDA:UniProtKB.
DR GO; GO:0004497; F:monooxygenase activity; IDA:UniProtKB.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IDA:UniProtKB.
DR GO; GO:0042440; P:pigment metabolic process; IDA:UniProtKB.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR002397; Cyt_P450_B.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00359; BP450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..404
FT /note="Biflaviolin synthase CYP158A2"
FT /id="PRO_0000430793"
FT BINDING 288
FT /ligand="flaviolin"
FT /ligand_id="ChEBI:CHEBI:58696"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:15659395,
FT ECO:0000269|PubMed:16239228, ECO:0007744|PDB:1T93,
FT ECO:0007744|PDB:2D09"
FT BINDING 288
FT /ligand="flaviolin"
FT /ligand_id="ChEBI:CHEBI:58696"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:15659395,
FT ECO:0000269|PubMed:16239228, ECO:0007744|PDB:1T93,
FT ECO:0007744|PDB:2D09"
FT BINDING 293
FT /ligand="flaviolin"
FT /ligand_id="ChEBI:CHEBI:58696"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:15659395,
FT ECO:0000269|PubMed:16239228, ECO:0007744|PDB:1T93,
FT ECO:0007744|PDB:2D09"
FT BINDING 353
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:15659395,
FT ECO:0000269|PubMed:16239228, ECO:0000269|PubMed:22203090,
FT ECO:0007744|PDB:1S1F, ECO:0007744|PDB:1SE6,
FT ECO:0007744|PDB:1T93, ECO:0007744|PDB:2D09,
FT ECO:0007744|PDB:2D0E, ECO:0007744|PDB:3TZO"
FT SITE 87
FT /note="Involved in determining product regiospecificity"
FT /evidence="ECO:0000269|PubMed:22203090"
FT MUTAGEN 87
FT /note="I->K: Catalyzes the formation of two isomers of
FT biflaviolin instead of three. Reduced affinity for
FT flaviolin."
FT /evidence="ECO:0000269|PubMed:22203090"
FT STRAND 13..15
FT /evidence="ECO:0007829|PDB:1S1F"
FT HELIX 28..36
FT /evidence="ECO:0007829|PDB:1S1F"
FT STRAND 38..43
FT /evidence="ECO:0007829|PDB:1S1F"
FT STRAND 45..49
FT /evidence="ECO:0007829|PDB:1S1F"
FT STRAND 51..54
FT /evidence="ECO:0007829|PDB:1S1F"
FT HELIX 57..64
FT /evidence="ECO:0007829|PDB:1S1F"
FT STRAND 69..71
FT /evidence="ECO:0007829|PDB:1S1F"
FT TURN 72..78
FT /evidence="ECO:0007829|PDB:1S1F"
FT STRAND 81..85
FT /evidence="ECO:0007829|PDB:1S1F"
FT STRAND 90..92
FT /evidence="ECO:0007829|PDB:1SE6"
FT HELIX 93..95
FT /evidence="ECO:0007829|PDB:1S1F"
FT HELIX 100..112
FT /evidence="ECO:0007829|PDB:1S1F"
FT HELIX 114..138
FT /evidence="ECO:0007829|PDB:1S1F"
FT STRAND 140..143
FT /evidence="ECO:0007829|PDB:1S1F"
FT HELIX 144..147
FT /evidence="ECO:0007829|PDB:1S1F"
FT TURN 148..150
FT /evidence="ECO:0007829|PDB:1S1F"
FT HELIX 151..161
FT /evidence="ECO:0007829|PDB:1S1F"
FT HELIX 165..167
FT /evidence="ECO:0007829|PDB:1S1F"
FT HELIX 168..182
FT /evidence="ECO:0007829|PDB:1S1F"
FT STRAND 183..186
FT /evidence="ECO:0007829|PDB:2D0E"
FT HELIX 189..192
FT /evidence="ECO:0007829|PDB:1S1F"
FT HELIX 194..204
FT /evidence="ECO:0007829|PDB:1S1F"
FT TURN 206..208
FT /evidence="ECO:0007829|PDB:3TZO"
FT HELIX 214..223
FT /evidence="ECO:0007829|PDB:1S1F"
FT HELIX 229..242
FT /evidence="ECO:0007829|PDB:1S1F"
FT HELIX 245..259
FT /evidence="ECO:0007829|PDB:1S1F"
FT HELIX 261..269
FT /evidence="ECO:0007829|PDB:1S1F"
FT HELIX 271..273
FT /evidence="ECO:0007829|PDB:1S1F"
FT HELIX 274..284
FT /evidence="ECO:0007829|PDB:1S1F"
FT STRAND 288..290
FT /evidence="ECO:0007829|PDB:1S1F"
FT STRAND 295..299
FT /evidence="ECO:0007829|PDB:1S1F"
FT STRAND 301..303
FT /evidence="ECO:0007829|PDB:1S1F"
FT STRAND 306..308
FT /evidence="ECO:0007829|PDB:1S1F"
FT STRAND 313..316
FT /evidence="ECO:0007829|PDB:1S1F"
FT HELIX 318..321
FT /evidence="ECO:0007829|PDB:1S1F"
FT TURN 325..327
FT /evidence="ECO:0007829|PDB:1S1F"
FT STRAND 328..330
FT /evidence="ECO:0007829|PDB:1S1F"
FT HELIX 356..373
FT /evidence="ECO:0007829|PDB:1S1F"
FT STRAND 378..381
FT /evidence="ECO:0007829|PDB:1S1F"
FT HELIX 383..385
FT /evidence="ECO:0007829|PDB:1S1F"
FT STRAND 401..403
FT /evidence="ECO:0007829|PDB:1S1F"
SQ SEQUENCE 404 AA; 44355 MW; D195F5C42B0A8E2B CRC64;
MTEETISQAV PPVRDWPAVD LPGSDFDPVL TELMREGPVT RISLPNGEGW AWLVTRHDDV
RLVTNDPRFG REAVMDRQVT RLAPHFIPAR GAVGFLDPPD HTRLRRSVAA AFTARGVERV
RERSRGMLDE LVDAMLRAGP PADLTEAVLS PFPIAVICEL MGVPATDRHS MHTWTQLILS
SSHGAEVSER AKNEMNAYFS DLIGLRSDSA GEDVTSLLGA AVGRDEITLS EAVGLAVLLQ
IGGEAVTNNS GQMFHLLLSR PELAERLRSE PEIRPRAIDE LLRWIPHRNA VGLSRIALED
VEIKGVRIRA GDAVYVSYLA ANRDPEVFPD PDRIDFERSP NPHVSFGFGP HYCPGGMLAR
LESELLVDAV LDRVPGLKLA VAPEDVPFKK GALIRGPEAL PVTW
