SGCE6_STRGL
ID SGCE6_STRGL Reviewed; 182 AA.
AC Q8GME2;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 71.
DE RecName: Full=NADH-dependent FAD reductase {ECO:0000305};
DE EC=1.5.1.37 {ECO:0000269|PubMed:19817865, ECO:0000305|PubMed:18426211};
DE AltName: Full=Antibiotic C-1027 biosynthesis two-component monooxygenase system, reductase component {ECO:0000305};
GN Name=sgcE6 {ECO:0000303|PubMed:12183628};
OS Streptomyces globisporus.
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=1908;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=C-1027;
RX PubMed=12183628; DOI=10.1126/science.1072110;
RA Liu W., Christenson S.D., Standage S., Shen B.;
RT "Biosynthesis of the enediyne antitumor antibiotic C-1027.";
RL Science 297:1170-1173(2002).
RN [2]
RP FUNCTION, ACTIVITY REGULATION, AND PATHWAY.
RX PubMed=18426211; DOI=10.1021/ja710601d;
RA Lin S., Van Lanen S.G., Shen B.;
RT "Characterization of the two-component, FAD-dependent monooxygenase SgcC
RT that requires carrier protein-tethered substrates for the biosynthesis of
RT the enediyne antitumor antibiotic C-1027.";
RL J. Am. Chem. Soc. 130:6616-6623(2008).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=19817865; DOI=10.1111/j.1574-6968.2009.01802.x;
RA Van Lanen S.G., Lin S., Horsman G.P., Shen B.;
RT "Characterization of SgcE6, the flavin reductase component supporting FAD-
RT dependent halogenation and hydroxylation in the biosynthesis of the
RT enediyne antitumor antibiotic C-1027.";
RL FEMS Microbiol. Lett. 300:237-241(2009).
RN [4] {ECO:0007744|PDB:4HX6, ECO:0007744|PDB:4R82}
RP X-RAY CRYSTALLOGRAPHY (1.66 ANGSTROMS) OF APOENZYME AND IN COMPLEX WITH FAD
RP AND NAD, AND SUBUNIT.
RX PubMed=27560143; DOI=10.1021/acs.biochem.6b00713;
RA Chang C.Y., Lohman J.R., Cao H., Tan K., Rudolf J.D., Ma M., Xu W.,
RA Bingman C.A., Yennamalli R.M., Bigelow L., Babnigg G., Yan X.,
RA Joachimiak A., Phillips G.N., Shen B.;
RT "Crystal structures of SgcE6 and SgcC, the two-component monooxygenase that
RT catalyzes hydroxylation of a carrier protein-tethered substrate during the
RT biosynthesis of the enediyne antitumor antibiotic C-1027 in Streptomyces
RT globisporus.";
RL Biochemistry 55:5142-5154(2016).
CC -!- FUNCTION: Reductase component of a two-component system involved in the
CC biosynthesis of the enediyne antitumor antibiotic C-1027
CC (PubMed:18426211, PubMed:19817865). SgcE6 provides the FADH(2) required
CC by both the halogenase SgcC3 and the monooxygenase SgcC through free
CC diffusion (PubMed:18426211, PubMed:19817865). Accepts only NADH and FAD
CC as substrates (PubMed:19817865). {ECO:0000269|PubMed:18426211,
CC ECO:0000269|PubMed:19817865}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=FADH2 + NAD(+) = FAD + 2 H(+) + NADH; Xref=Rhea:RHEA:30147,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57692,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:58307; EC=1.5.1.37;
CC Evidence={ECO:0000269|PubMed:19817865, ECO:0000305|PubMed:18426211};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:30149;
CC Evidence={ECO:0000269|PubMed:19817865, ECO:0000305|PubMed:18426211};
CC -!- ACTIVITY REGULATION: The SgcE6-SgcC hydroxylation activity decreases in
CC the presence of excess FAD. {ECO:0000269|PubMed:18426211}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=53 uM for NADH {ECO:0000269|PubMed:19817865};
CC KM=8.2 uM for FAD {ECO:0000269|PubMed:19817865};
CC Note=kcat is 3.1 sec(-1) with NADH as substrate. kcat is 4.5 sec(-1)
CC with FAD as substrate. {ECO:0000269|PubMed:19817865};
CC -!- PATHWAY: Antibiotic biosynthesis. {ECO:0000269|PubMed:18426211}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:27560143}.
CC -!- SIMILARITY: Belongs to the non-flavoprotein flavin reductase family.
CC {ECO:0000305}.
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DR EMBL; AY048670; AAL06698.1; -; Genomic_DNA.
DR PDB; 4HX6; X-ray; 1.89 A; A/B/C/D/E/F/G/H=1-182.
DR PDB; 4R82; X-ray; 1.66 A; A/B=1-182.
DR PDBsum; 4HX6; -.
DR PDBsum; 4R82; -.
DR SMR; Q8GME2; -.
DR BRENDA; 1.14.14.15; 5933.
DR BRENDA; 1.5.1.37; 5933.
DR GO; GO:0010181; F:FMN binding; IEA:InterPro.
DR GO; GO:0016646; F:oxidoreductase activity, acting on the CH-NH group of donors, NAD or NADP as acceptor; IEA:UniProt.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR Gene3D; 2.30.110.10; -; 1.
DR InterPro; IPR002563; Flavin_Rdtase-like_dom.
DR InterPro; IPR012349; Split_barrel_FMN-bd.
DR Pfam; PF01613; Flavin_Reduct; 1.
DR SMART; SM00903; Flavin_Reduct; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic biosynthesis; FAD; Flavoprotein; NAD;
KW Nucleotide-binding; Oxidoreductase.
FT CHAIN 1..182
FT /note="NADH-dependent FAD reductase"
FT /id="PRO_0000454945"
FT BINDING 16
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:27560143,
FT ECO:0007744|PDB:4R82"
FT BINDING 47..48
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:27560143,
FT ECO:0007744|PDB:4R82"
FT BINDING 62..64
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:27560143,
FT ECO:0007744|PDB:4R82"
FT BINDING 98
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:27560143,
FT ECO:0007744|PDB:4R82"
FT BINDING 143
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:27560143,
FT ECO:0007744|PDB:4R82"
FT HELIX 2..5
FT /evidence="ECO:0007829|PDB:4HX6"
FT STRAND 10..12
FT /evidence="ECO:0007829|PDB:4R82"
FT HELIX 17..24
FT /evidence="ECO:0007829|PDB:4R82"
FT STRAND 32..36
FT /evidence="ECO:0007829|PDB:4R82"
FT STRAND 38..40
FT /evidence="ECO:0007829|PDB:4R82"
FT STRAND 42..47
FT /evidence="ECO:0007829|PDB:4R82"
FT STRAND 50..53
FT /evidence="ECO:0007829|PDB:4R82"
FT TURN 54..57
FT /evidence="ECO:0007829|PDB:4R82"
FT STRAND 58..64
FT /evidence="ECO:0007829|PDB:4R82"
FT HELIX 68..75
FT /evidence="ECO:0007829|PDB:4R82"
FT STRAND 77..83
FT /evidence="ECO:0007829|PDB:4R82"
FT HELIX 89..94
FT /evidence="ECO:0007829|PDB:4R82"
FT STRAND 108..110
FT /evidence="ECO:0007829|PDB:4R82"
FT STRAND 112..114
FT /evidence="ECO:0007829|PDB:4R82"
FT TURN 116..118
FT /evidence="ECO:0007829|PDB:4R82"
FT STRAND 121..123
FT /evidence="ECO:0007829|PDB:4R82"
FT STRAND 127..140
FT /evidence="ECO:0007829|PDB:4R82"
FT STRAND 143..155
FT /evidence="ECO:0007829|PDB:4R82"
FT STRAND 163..165
FT /evidence="ECO:0007829|PDB:4R82"
FT STRAND 168..170
FT /evidence="ECO:0007829|PDB:4R82"
SQ SEQUENCE 182 AA; 19486 MW; 2A618B7FB2FDA1A1 CRC64;
MSPIIAPPAE LVDPKDRVQL RRVFGDFPTG VTVVTVGGSE PRGMTANSFT SVSLSPPLVL
ICVGKDAVMH QRLTALPTFA VSVLEAGQEK AARHFADHSR PPGVDQFDTV DWVLGEESGA
PLIAGAVAHL ECAIHRLYEG GDHTIFLGEV ITATRWPARE GMLFSGGRFR RFAPDADEGR
AA
