SGCC_STRGL
ID SGCC_STRGL Reviewed; 527 AA.
AC Q8GMG6;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 75.
DE RecName: Full=(3S)-3-amino-3-(3-chloro-4-hydroxyphenyl)propanoyl-[peptidyl-carrier protein SgcC2] monooxygenase {ECO:0000305};
DE EC=1.14.14.15 {ECO:0000269|PubMed:18426211};
DE AltName: Full=Antibiotic C-1027 biosynthesis two-component monooxygenase system, oxygenase component {ECO:0000305};
GN Name=sgcC {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], PATHWAY, AND DISRUPTION PHENOTYPE.
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, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, 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] {ECO:0007744|PDB:4OO2}
RP X-RAY CRYSTALLOGRAPHY (2.63 ANGSTROMS), 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: Oxygenase component of a two-component system involved in the
CC biosynthesis of the enediyne antitumor antibiotic C-1027
CC (PubMed:18426211). Uses FADH(2) supplied by SgcE6 to catalyze the C-5
CC hydroxylation of (S)-3-chloro-beta-tyrosyl-S-SgcC2 (PubMed:18426211).
CC Can also efficiently catalyze the regioselective hydroxylation of other
CC 3-substituted beta-tyrosyl-S-SgcC2 analogs, including the bromo-,
CC iodo-, fluoro-, and methyl-substituted analogs, but does not accept 3-
CC hydroxy-beta-tyrosyl-S-SgcC2 as a substrate (PubMed:18426211). Is only
CC active with SgcC2 (peptidyl carrier protein)-tethered substrates
CC (PubMed:18426211). {ECO:0000269|PubMed:18426211}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-3-amino-3-(3-chloro-4-hydroxyphenyl)propanoyl-[SgcC2
CC peptidyl-carrier protein] + FADH2 + O2 = (3S)-3-amino-3-(3-chloro-
CC 4,5-dihydroxyphenyl)propanoyl-[SgcC2 peptidyl-carrier protein] + FAD
CC + H(+) + H2O; Xref=Rhea:RHEA:41560, Rhea:RHEA-COMP:9805, Rhea:RHEA-
CC COMP:9806, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57692, ChEBI:CHEBI:58307, ChEBI:CHEBI:78296,
CC ChEBI:CHEBI:78297; EC=1.14.14.15;
CC Evidence={ECO:0000269|PubMed:18426211};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41561;
CC Evidence={ECO:0000269|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=742 uM for (S)-3-chloro-beta-tyrosinyl-S-SgcC2
CC {ECO:0000269|PubMed:18426211};
CC Note=kcat is 1.4 min(-1). {ECO:0000269|PubMed:18426211};
CC pH dependence:
CC Optimum pH is 6.0. {ECO:0000269|PubMed:18426211};
CC -!- PATHWAY: Antibiotic biosynthesis. {ECO:0000269|PubMed:12183628,
CC ECO:0000269|PubMed:18426211}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:27560143}.
CC -!- DISRUPTION PHENOTYPE: Disruption of the gene abolishes C-1027
CC production and leads to the formation of 22-deshydroxy-C-1027.
CC {ECO:0000269|PubMed:12183628}.
CC -!- SIMILARITY: Belongs to the FADH(2)-utilizing monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; AY048670; AAL06674.1; -; Genomic_DNA.
DR PDB; 4OO2; X-ray; 2.63 A; A/B/C/D=1-527.
DR PDBsum; 4OO2; -.
DR SMR; Q8GMG6; -.
DR BRENDA; 1.14.14.15; 5933.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016627; F:oxidoreductase activity, acting on the CH-CH group of donors; IEA:InterPro.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR Gene3D; 2.40.110.10; -; 1.
DR InterPro; IPR046373; Acyl-CoA_Oxase/DH_mid-dom_sf.
DR InterPro; IPR036250; AcylCo_DH-like_C.
DR InterPro; IPR009100; AcylCoA_DH/oxidase_NM_dom.
DR InterPro; IPR024677; HpaB/PvcC.
DR InterPro; IPR004925; HpaB/PvcC/4-BUDH.
DR InterPro; IPR024719; HpaB/PvcC/4-BUDH_C.
DR InterPro; IPR024674; HpaB/PvcC/4-BUDH_N.
DR PANTHER; PTHR36117; PTHR36117; 1.
DR Pfam; PF03241; HpaB; 1.
DR Pfam; PF11794; HpaB_N; 1.
DR PIRSF; PIRSF500125; 4_HPA_large; 1.
DR PIRSF; PIRSF000331; HpaA_HpaB; 1.
DR SUPFAM; SSF47203; SSF47203; 1.
DR SUPFAM; SSF56645; SSF56645; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic biosynthesis; FAD; Flavoprotein; Monooxygenase;
KW Oxidoreductase.
FT CHAIN 1..527
FT /note="(3S)-3-amino-3-(3-chloro-4-hydroxyphenyl)propanoyl-
FT [peptidyl-carrier protein SgcC2] monooxygenase"
FT /id="PRO_0000454946"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 161..163
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q5SJP8"
FT BINDING 167..170
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q5SJP8"
FT BINDING 202
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q5SJP8"
FT HELIX 23..30
FT /evidence="ECO:0007829|PDB:4OO2"
FT STRAND 31..33
FT /evidence="ECO:0007829|PDB:4OO2"
FT STRAND 35..38
FT /evidence="ECO:0007829|PDB:4OO2"
FT TURN 46..48
FT /evidence="ECO:0007829|PDB:4OO2"
FT TURN 50..52
FT /evidence="ECO:0007829|PDB:4OO2"
FT HELIX 53..65
FT /evidence="ECO:0007829|PDB:4OO2"
FT HELIX 72..75
FT /evidence="ECO:0007829|PDB:4OO2"
FT STRAND 76..78
FT /evidence="ECO:0007829|PDB:4OO2"
FT STRAND 80..87
FT /evidence="ECO:0007829|PDB:4OO2"
FT HELIX 88..90
FT /evidence="ECO:0007829|PDB:4OO2"
FT HELIX 96..112
FT /evidence="ECO:0007829|PDB:4OO2"
FT TURN 113..115
FT /evidence="ECO:0007829|PDB:4OO2"
FT TURN 121..124
FT /evidence="ECO:0007829|PDB:4OO2"
FT HELIX 125..128
FT /evidence="ECO:0007829|PDB:4OO2"
FT TURN 129..134
FT /evidence="ECO:0007829|PDB:4OO2"
FT HELIX 136..138
FT /evidence="ECO:0007829|PDB:4OO2"
FT TURN 139..141
FT /evidence="ECO:0007829|PDB:4OO2"
FT HELIX 142..155
FT /evidence="ECO:0007829|PDB:4OO2"
FT STRAND 159..162
FT /evidence="ECO:0007829|PDB:4OO2"
FT STRAND 183..186
FT /evidence="ECO:0007829|PDB:4OO2"
FT STRAND 189..202
FT /evidence="ECO:0007829|PDB:4OO2"
FT HELIX 204..206
FT /evidence="ECO:0007829|PDB:4OO2"
FT STRAND 208..212
FT /evidence="ECO:0007829|PDB:4OO2"
FT HELIX 222..224
FT /evidence="ECO:0007829|PDB:4OO2"
FT STRAND 226..231
FT /evidence="ECO:0007829|PDB:4OO2"
FT STRAND 237..240
FT /evidence="ECO:0007829|PDB:4OO2"
FT HELIX 245..252
FT /evidence="ECO:0007829|PDB:4OO2"
FT TURN 255..257
FT /evidence="ECO:0007829|PDB:4OO2"
FT HELIX 261..264
FT /evidence="ECO:0007829|PDB:4OO2"
FT STRAND 268..279
FT /evidence="ECO:0007829|PDB:4OO2"
FT HELIX 280..282
FT /evidence="ECO:0007829|PDB:4OO2"
FT STRAND 283..287
FT /evidence="ECO:0007829|PDB:4OO2"
FT HELIX 289..298
FT /evidence="ECO:0007829|PDB:4OO2"
FT HELIX 301..331
FT /evidence="ECO:0007829|PDB:4OO2"
FT HELIX 333..335
FT /evidence="ECO:0007829|PDB:4OO2"
FT HELIX 337..362
FT /evidence="ECO:0007829|PDB:4OO2"
FT HELIX 368..370
FT /evidence="ECO:0007829|PDB:4OO2"
FT HELIX 376..400
FT /evidence="ECO:0007829|PDB:4OO2"
FT HELIX 402..405
FT /evidence="ECO:0007829|PDB:4OO2"
FT HELIX 413..416
FT /evidence="ECO:0007829|PDB:4OO2"
FT TURN 418..420
FT /evidence="ECO:0007829|PDB:4OO2"
FT HELIX 421..427
FT /evidence="ECO:0007829|PDB:4OO2"
FT HELIX 436..450
FT /evidence="ECO:0007829|PDB:4OO2"
FT HELIX 453..464
FT /evidence="ECO:0007829|PDB:4OO2"
FT STRAND 465..467
FT /evidence="ECO:0007829|PDB:4OO2"
FT HELIX 471..482
FT /evidence="ECO:0007829|PDB:4OO2"
FT HELIX 485..497
FT /evidence="ECO:0007829|PDB:4OO2"
FT HELIX 514..521
FT /evidence="ECO:0007829|PDB:4OO2"
FT HELIX 522..524
FT /evidence="ECO:0007829|PDB:4OO2"
SQ SEQUENCE 527 AA; 58255 MW; 08619D240A0932A9 CRC64;
MPHGAEREAS PAEESAGTRP LTGEEYLESL RDAREVYLDG SRVKDVTAHP AFHNPARMTA
RLYDSLHDPA QKAVLTAPTD AGDGFTHRFF TAPRSVDDLV KDQAAIASWA RKSYGWMGRS
PDYKASFLGT LGANADFYEP FADNARRWYR ESQEKVLYWN HAFLHPPVDR SLPADEVGDV
FIHVERETDA GLVVSGAKVV ATGSALTHAA FISHWGLPIK DRKFALVATV PMDADGLKVI
CRPSYSANAA TTGSPFDNPL SSRLDENDAI LVLDQVLIPW ENVFVYGNLG KVHLLAGQSG
MIERATFHGC TRLAVKLEFI AGLLAKALDI TGAKDFRGVQ TRLGEVLAWR NLFWSLSDAA
ARNPVPWKNG TLLPNPQAGM AYRWFMQIGY PRVLEIVQQD VASGLMYVNS STEDFRNPET
GPYLEKYLRG SDGAGAVERV KVMKLLWDAV GSDFGGRHEL YERNYSGNHE NTRIELLLSQ
TASGKLDSYM DFAQACMDEY DLDGWTAPDL ESFHAMRSAS RDLLGGL
