MYCG_MICGR
ID MYCG_MICGR Reviewed; 397 AA.
AC Q59523;
DT 11-NOV-2015, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 91.
DE RecName: Full=Mycinamicin IV hydroxylase/epoxidase {ECO:0000305|PubMed:18804032};
DE EC=1.14.-.- {ECO:0000269|PubMed:18804032};
DE AltName: Full=Cytochrome P450 MycG {ECO:0000303|PubMed:18804032};
DE AltName: Full=Multifunctional P450 enzyme {ECO:0000303|PubMed:22547618};
DE AltName: Full=Mycinamicin biosynthesis protein G {ECO:0000305|PubMed:18804032};
GN Name=mycG {ECO:0000303|PubMed:18804032};
OS Micromonospora griseorubida.
OC Bacteria; Actinobacteria; Micromonosporales; Micromonosporaceae;
OC Micromonospora.
OX NCBI_TaxID=28040;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=A11725 {ECO:0000312|EMBL:BAA03672.1};
RX PubMed=7808395; DOI=10.1007/bf00302258;
RA Inouye M., Takada Y., Muto N., Horinouchi S., Beppu T.;
RT "Characterization and expression of a P-450-like mycinamicin biosynthesis
RT gene using a novel Micromonospora-Escherichia coli shuttle cosmid vector.";
RL Mol. Gen. Genet. 245:456-464(1994).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND PATHWAY.
RX PubMed=18804032; DOI=10.1016/j.chembiol.2008.07.014;
RA Anzai Y., Li S., Chaulagain M.R., Kinoshita K., Kato F., Montgomery J.,
RA Sherman D.H.;
RT "Functional analysis of MycCI and MycG, cytochrome P450 enzymes involved in
RT biosynthesis of mycinamicin macrolide antibiotics.";
RL Chem. Biol. 15:950-959(2008).
RN [3]
RP FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RC STRAIN=A11725;
RX PubMed=22547618; DOI=10.1128/aac.06063-11;
RA Anzai Y., Tsukada S., Sakai A., Masuda R., Harada C., Domeki A., Li S.,
RA Kinoshita K., Sherman D.H., Kato F.;
RT "Function of cytochrome P450 enzymes MycCI and MycG in Micromonospora
RT griseorubida, a producer of the macrolide antibiotic mycinamicin.";
RL Antimicrob. Agents Chemother. 56:3648-3656(2012).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.62 ANGSTROMS) OF WILD-TYPE AND MUTANTS ALA-286 AND
RP VAL-286 IN COMPLEXES WITH HEME; MYCINAMICIN III; MYCINAMICIN IV AND
RP MYCINAMICIN V, COFACTOR, AND MUTAGENESIS OF PHE-286.
RX PubMed=22952225; DOI=10.1074/jbc.m112.410340;
RA Li S., Tietz D.R., Rutaganira F.U., Kells P.M., Anzai Y., Kato F.,
RA Pochapsky T.C., Sherman D.H., Podust L.M.;
RT "Substrate recognition by the multifunctional cytochrome P450 MycG in
RT mycinamicin hydroxylation and epoxidation reactions.";
RL J. Biol. Chem. 287:37880-37890(2012).
CC -!- FUNCTION: Involved in the biosynthesis of mycinamicin, a 16-membered
CC macrolide antibiotic. Catalyzes consecutive hydroxylation (at C14) and
CC epoxidation (at C12-C13) reactions with mycinamicin IV as initial
CC substrate, leading to mycinamicin II. These reactions require prior
CC dimethylation of 6-deoxyallose to mycinose for effective conversion by
CC the dual function MycG enzyme. {ECO:0000269|PubMed:18804032,
CC ECO:0000269|PubMed:22547618, ECO:0000269|PubMed:7808395}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000269|PubMed:22952225};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=16.2 uM for mycinamicin V {ECO:0000269|PubMed:18804032};
CC Note=kcat is 415.7 min(-1) for the epoxydation of mycinamicin V.
CC {ECO:0000269|PubMed:18804032};
CC -!- PATHWAY: Antibiotic biosynthesis; mycinamicin biosynthesis.
CC {ECO:0000269|PubMed:22547618, ECO:0000305|PubMed:18804032}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene do not produce
CC mycinamicin I, mycinamicin II and mycinamicin V, and accumulate
CC mycinamicin IV. {ECO:0000269|PubMed:22547618}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; D16098; BAA03672.1; -; Genomic_DNA.
DR PIR; S51594; S51594.
DR PDB; 2Y46; X-ray; 1.83 A; A/B/C=1-397.
DR PDB; 2Y5N; X-ray; 1.62 A; A/B=1-397.
DR PDB; 2Y5Z; X-ray; 2.06 A; A/B/C=1-397.
DR PDB; 2Y98; X-ray; 1.65 A; A=1-397.
DR PDB; 2YCA; X-ray; 1.80 A; A=1-397.
DR PDB; 2YGX; X-ray; 2.39 A; A/B/C/D=1-397.
DR PDB; 3ZSN; X-ray; 1.90 A; A/B/C=1-397.
DR PDB; 4AW3; X-ray; 2.05 A; A/B=1-397.
DR PDB; 5UHU; NMR; -; A=1-397.
DR PDBsum; 2Y46; -.
DR PDBsum; 2Y5N; -.
DR PDBsum; 2Y5Z; -.
DR PDBsum; 2Y98; -.
DR PDBsum; 2YCA; -.
DR PDBsum; 2YGX; -.
DR PDBsum; 3ZSN; -.
DR PDBsum; 4AW3; -.
DR PDBsum; 5UHU; -.
DR AlphaFoldDB; Q59523; -.
DR BMRB; Q59523; -.
DR SMR; Q59523; -.
DR KEGG; ag:BAA03672; -.
DR BioCyc; MetaCyc:MON-18369; -.
DR UniPathway; UPA01019; -.
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; IEA:InterPro.
DR GO; GO:0017000; P:antibiotic biosynthetic 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; 2.
DR PRINTS; PR00359; BP450.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic biosynthesis; Heme; Iron; Metal-binding;
KW Monooxygenase; NADP; Oxidoreductase.
FT CHAIN 1..397
FT /note="Mycinamicin IV hydroxylase/epoxidase"
FT /id="PRO_0000434765"
FT REGION 63..86
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 81
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:22952225,
FT ECO:0007744|PDB:2Y46, ECO:0007744|PDB:2Y98,
FT ECO:0007744|PDB:3ZSN"
FT BINDING 91
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /evidence="ECO:0000269|PubMed:22952225"
FT BINDING 95
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /evidence="ECO:0000269|PubMed:22952225"
FT BINDING 288
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /evidence="ECO:0000269|PubMed:22952225"
FT BINDING 344
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /evidence="ECO:0000269|PubMed:22952225"
FT BINDING 346
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:22952225,
FT ECO:0007744|PDB:2Y5N, ECO:0007744|PDB:2Y98,
FT ECO:0007744|PDB:2YCA"
FT MUTAGEN 286
FT /note="F->A,V: Decrease in catalytic activity."
FT /evidence="ECO:0000269|PubMed:22952225"
FT STRAND 6..9
FT /evidence="ECO:0007829|PDB:2Y5N"
FT STRAND 14..16
FT /evidence="ECO:0007829|PDB:2Y5N"
FT HELIX 21..29
FT /evidence="ECO:0007829|PDB:2Y5N"
FT STRAND 31..36
FT /evidence="ECO:0007829|PDB:2Y5N"
FT STRAND 38..40
FT /evidence="ECO:0007829|PDB:2Y5N"
FT STRAND 43..46
FT /evidence="ECO:0007829|PDB:2Y5N"
FT HELIX 49..56
FT /evidence="ECO:0007829|PDB:2Y5N"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:2Y5N"
FT HELIX 64..67
FT /evidence="ECO:0007829|PDB:2Y5N"
FT STRAND 73..77
FT /evidence="ECO:0007829|PDB:2Y5N"
FT HELIX 83..85
FT /evidence="ECO:0007829|PDB:2Y5N"
FT HELIX 90..101
FT /evidence="ECO:0007829|PDB:2Y5N"
FT HELIX 104..109
FT /evidence="ECO:0007829|PDB:2Y5N"
FT HELIX 111..128
FT /evidence="ECO:0007829|PDB:2Y5N"
FT STRAND 130..133
FT /evidence="ECO:0007829|PDB:2Y5N"
FT HELIX 134..137
FT /evidence="ECO:0007829|PDB:2Y5N"
FT TURN 138..141
FT /evidence="ECO:0007829|PDB:2Y5N"
FT HELIX 142..151
FT /evidence="ECO:0007829|PDB:2Y5N"
FT HELIX 155..157
FT /evidence="ECO:0007829|PDB:2Y5N"
FT HELIX 158..166
FT /evidence="ECO:0007829|PDB:2Y5N"
FT STRAND 170..172
FT /evidence="ECO:0007829|PDB:5UHU"
FT HELIX 176..199
FT /evidence="ECO:0007829|PDB:2Y5N"
FT HELIX 205..211
FT /evidence="ECO:0007829|PDB:2Y5N"
FT HELIX 221..252
FT /evidence="ECO:0007829|PDB:2Y5N"
FT HELIX 254..262
FT /evidence="ECO:0007829|PDB:2Y5N"
FT HELIX 264..266
FT /evidence="ECO:0007829|PDB:2Y5N"
FT HELIX 267..277
FT /evidence="ECO:0007829|PDB:2Y5N"
FT STRAND 281..283
FT /evidence="ECO:0007829|PDB:2Y5N"
FT STRAND 288..292
FT /evidence="ECO:0007829|PDB:2Y5N"
FT STRAND 294..296
FT /evidence="ECO:0007829|PDB:2Y5N"
FT STRAND 299..301
FT /evidence="ECO:0007829|PDB:2Y5N"
FT STRAND 306..309
FT /evidence="ECO:0007829|PDB:2Y5N"
FT HELIX 311..314
FT /evidence="ECO:0007829|PDB:2Y5N"
FT TURN 318..320
FT /evidence="ECO:0007829|PDB:2Y5N"
FT TURN 322..325
FT /evidence="ECO:0007829|PDB:2Y5N"
FT HELIX 342..344
FT /evidence="ECO:0007829|PDB:2YCA"
FT HELIX 349..366
FT /evidence="ECO:0007829|PDB:2Y5N"
FT STRAND 371..374
FT /evidence="ECO:0007829|PDB:2Y5N"
FT HELIX 376..378
FT /evidence="ECO:0007829|PDB:2Y5N"
FT STRAND 385..387
FT /evidence="ECO:0007829|PDB:2Y5N"
FT STRAND 394..396
FT /evidence="ECO:0007829|PDB:2Y5N"
SQ SEQUENCE 397 AA; 44332 MW; 0FE6A251BEB5E233 CRC64;
MTSAEPRAYP FNDVHGLTLA GRYGELQETE PVSRVRPPYG EEAWLVTRYE DVRAVLGDGR
FVRGPSMTRD EPRTRPEMVK GGLLSMDPPE HSRLRRLVVK AFTARRAESL RPRAREIAHE
LVDQMAATGQ PADLVAMFAR QLPVRVICEL LGVPSADHDR FTRWSGAFLS TAEVTAEEMQ
EAAEQAYAYM GDLIDRRRKE PTDDLVSALV QARDQQDSLS EQELLDLAIG LLVAGYESTT
TQIADFVYLL MTRPELRRQL LDRPELIPSA VEELTRWVPL GVGTAFPRYA VEDVTLRGVT
IRAGEPVLAS TGAANRDQAQ FPDADRIDVD RTPNQHLGFG HGVHHCLGAP LARVELQVAL
EVLLQRLPGI RLGIPETQLR WSEGMLLRGP LELPVVW
