OXYS_STRR1
ID OXYS_STRR1 Reviewed; 503 AA.
AC L8EUQ6;
DT 28-MAR-2018, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2013, sequence version 1.
DT 03-AUG-2022, entry version 49.
DE RecName: Full=12-dehydrotetracycline 5-monooxygenase/anhydrotetracycline 6-monooxygenase {ECO:0000303|PubMed:23621493};
DE EC=1.14.13.234 {ECO:0000269|PubMed:23621493};
DE EC=1.14.13.38 {ECO:0000269|PubMed:23621493};
GN Name=oxyS {ECO:0000312|EMBL:ELQ83303.1};
GN ORFNames=SRIM_10936 {ECO:0000312|EMBL:ELQ83303.1};
OS Streptomyces rimosus subsp. rimosus (strain ATCC 10970 / DSM 40260 / JCM
OS 4667 / NRRL 2234).
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=1265868;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 10970 / DSM 40260 / JCM 4667 / NRRL 2234;
RX PubMed=23516198; DOI=10.1128/genomea.00063-13;
RA Pethick F.E., MacFadyen A.C., Tang Z., Sangal V., Liu T.-T., Chu J.,
RA Kosec G., Petkovic H., Guo M., Kirby R., Hoskisson P.A., Herron P.R.,
RA Hunter I.S.;
RT "Draft genome sequence of the oxytetracycline-producing bacterium
RT Streptomyces rimosus ATCC 10970.";
RL Genome Announc. 1:E00063-E00063(2013).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) IN COMPLEX WITH FAD, FUNCTION,
RP CATALYTIC ACTIVITY, MUTAGENESIS OF HIS-47 AND PHE-215, COFACTOR, SUBUNIT,
RP AND PATHWAY.
RC STRAIN=ATCC 10970 / DSM 40260 / JCM 4667 / NRRL 2234;
RX PubMed=23621493; DOI=10.1021/ja403516u;
RA Wang P., Bashiri G., Gao X., Sawaya M.R., Tang Y.;
RT "Uncovering the enzymes that catalyze the final steps in oxytetracycline
RT biosynthesis.";
RL J. Am. Chem. Soc. 135:7138-7141(2013).
CC -!- FUNCTION: Involved in the biosynthesis of the antibiotics
CC oxytetracycline and tetracycline. OxyS starts by catalyzing the
CC stereospecific hydroxylation of anhydrotetracycline at C(6) position to
CC yield 5a,11a-dehydrotetracycline (12-dehydrotetracycline). If the
CC released product is captured by OxyR, it is reduced to tetracycline.
CC However, if the released product is recaptured by OxyS, it performs an
CC additional hydroxylation at C(5), producing 5a,11a-
CC dehydrooxytetracycline, which, following the action of OxyR becomes
CC oxytetracycline. {ECO:0000269|PubMed:23621493}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5a,11a-dehydrotetracycline + H(+) + NADPH + O2 = 5a,11a-
CC dehydrooxytetracycline + H2O + NADP(+); Xref=Rhea:RHEA:50388,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57522, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:133012; EC=1.14.13.234;
CC Evidence={ECO:0000269|PubMed:23621493};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=anhydrotetracycline + H(+) + NADPH + O2 = 5a,11a-
CC dehydrotetracycline + H2O + NADP(+); Xref=Rhea:RHEA:11976,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57522, ChEBI:CHEBI:57783, ChEBI:CHEBI:58032,
CC ChEBI:CHEBI:58349; EC=1.14.13.38;
CC Evidence={ECO:0000269|PubMed:23621493};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:23621493};
CC Note=Binds 1 FAD per subunit. {ECO:0000269|PubMed:23621493};
CC -!- PATHWAY: Antibiotic biosynthesis; oxytetracycline biosynthesis.
CC {ECO:0000305|PubMed:23621493}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:23621493}.
CC -!- SIMILARITY: Belongs to the PheA/TfdB FAD monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; ANSJ01000024; ELQ83303.1; -; Genomic_DNA.
DR RefSeq; WP_003981036.1; NZ_ANSJ01000024.1.
DR PDB; 4K2X; X-ray; 2.55 A; A/B=1-503.
DR PDBsum; 4K2X; -.
DR AlphaFoldDB; L8EUQ6; -.
DR SMR; L8EUQ6; -.
DR EnsemblBacteria; ELQ83303; ELQ83303; SRIM_10936.
DR GeneID; 66859920; -.
DR PATRIC; fig|1265868.3.peg.2256; -.
DR OMA; LYKFMGV; -.
DR BioCyc; MetaCyc:MON-19943; -.
DR BRENDA; 1.14.13.234; 14570.
DR UniPathway; UPA00926; -.
DR GO; GO:0047670; F:anhydrotetracycline monooxygenase activity; IEA:UniProtKB-EC.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR Gene3D; 3.50.50.60; -; 2.
DR InterPro; IPR002938; FAD-bd.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR Pfam; PF01494; FAD_binding_3; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic biosynthesis; FAD; Flavoprotein; Monooxygenase;
KW NADP; Nucleotide-binding; Oxidoreductase.
FT CHAIN 1..503
FT /note="12-dehydrotetracycline 5-
FT monooxygenase/anhydrotetracycline 6-monooxygenase"
FT /id="PRO_0000443522"
FT BINDING 13
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:23621493,
FT ECO:0007744|PDB:4K2X"
FT BINDING 32..33
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:23621493,
FT ECO:0007744|PDB:4K2X"
FT BINDING 44
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:23621493,
FT ECO:0007744|PDB:4K2X"
FT BINDING 99
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:23621493,
FT ECO:0007744|PDB:4K2X"
FT BINDING 123
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:23621493,
FT ECO:0007744|PDB:4K2X"
FT BINDING 160
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:23621493,
FT ECO:0007744|PDB:4K2X"
FT BINDING 288
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:23621493,
FT ECO:0007744|PDB:4K2X"
FT BINDING 301..302
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:23621493,
FT ECO:0007744|PDB:4K2X"
FT MUTAGEN 47
FT /note="H->A: Decrease of the ratio between oxytetracycline
FT and tetracycline."
FT /evidence="ECO:0000269|PubMed:23621493"
FT MUTAGEN 215
FT /note="F->I: Dramatic change in the product ratio, in which
FT the amount of tetracycline exceeds that of
FT oxytetracycline."
FT /evidence="ECO:0000269|PubMed:23621493"
FT STRAND 4..8
FT /evidence="ECO:0007829|PDB:4K2X"
FT HELIX 12..23
FT /evidence="ECO:0007829|PDB:4K2X"
FT STRAND 28..33
FT /evidence="ECO:0007829|PDB:4K2X"
FT HELIX 48..56
FT /evidence="ECO:0007829|PDB:4K2X"
FT HELIX 60..64
FT /evidence="ECO:0007829|PDB:4K2X"
FT STRAND 87..90
FT /evidence="ECO:0007829|PDB:4K2X"
FT STRAND 93..95
FT /evidence="ECO:0007829|PDB:4K2X"
FT HELIX 99..112
FT /evidence="ECO:0007829|PDB:4K2X"
FT STRAND 116..119
FT /evidence="ECO:0007829|PDB:4K2X"
FT STRAND 122..128
FT /evidence="ECO:0007829|PDB:4K2X"
FT STRAND 133..139
FT /evidence="ECO:0007829|PDB:4K2X"
FT STRAND 142..153
FT /evidence="ECO:0007829|PDB:4K2X"
FT HELIX 160..165
FT /evidence="ECO:0007829|PDB:4K2X"
FT STRAND 175..187
FT /evidence="ECO:0007829|PDB:4K2X"
FT STRAND 201..205
FT /evidence="ECO:0007829|PDB:4K2X"
FT TURN 206..209
FT /evidence="ECO:0007829|PDB:4K2X"
FT STRAND 210..218
FT /evidence="ECO:0007829|PDB:4K2X"
FT STRAND 221..229
FT /evidence="ECO:0007829|PDB:4K2X"
FT HELIX 242..253
FT /evidence="ECO:0007829|PDB:4K2X"
FT STRAND 259..269
FT /evidence="ECO:0007829|PDB:4K2X"
FT STRAND 272..274
FT /evidence="ECO:0007829|PDB:4K2X"
FT STRAND 278..280
FT /evidence="ECO:0007829|PDB:4K2X"
FT STRAND 283..285
FT /evidence="ECO:0007829|PDB:4K2X"
FT HELIX 287..289
FT /evidence="ECO:0007829|PDB:4K2X"
FT HELIX 300..319
FT /evidence="ECO:0007829|PDB:4K2X"
FT TURN 325..329
FT /evidence="ECO:0007829|PDB:4K2X"
FT HELIX 330..352
FT /evidence="ECO:0007829|PDB:4K2X"
FT HELIX 357..359
FT /evidence="ECO:0007829|PDB:4K2X"
FT HELIX 360..370
FT /evidence="ECO:0007829|PDB:4K2X"
FT HELIX 373..384
FT /evidence="ECO:0007829|PDB:4K2X"
FT STRAND 393..395
FT /evidence="ECO:0007829|PDB:4K2X"
FT TURN 397..400
FT /evidence="ECO:0007829|PDB:4K2X"
FT STRAND 407..410
FT /evidence="ECO:0007829|PDB:4K2X"
FT STRAND 413..416
FT /evidence="ECO:0007829|PDB:4K2X"
FT HELIX 417..420
FT /evidence="ECO:0007829|PDB:4K2X"
FT STRAND 426..433
FT /evidence="ECO:0007829|PDB:4K2X"
FT HELIX 436..441
FT /evidence="ECO:0007829|PDB:4K2X"
FT HELIX 442..444
FT /evidence="ECO:0007829|PDB:4K2X"
FT TURN 445..447
FT /evidence="ECO:0007829|PDB:4K2X"
FT STRAND 448..457
FT /evidence="ECO:0007829|PDB:4K2X"
FT TURN 462..465
FT /evidence="ECO:0007829|PDB:4K2X"
FT STRAND 467..471
FT /evidence="ECO:0007829|PDB:4K2X"
FT STRAND 475..481
FT /evidence="ECO:0007829|PDB:4K2X"
FT TURN 483..485
FT /evidence="ECO:0007829|PDB:4K2X"
FT HELIX 490..498
FT /evidence="ECO:0007829|PDB:4K2X"
SQ SEQUENCE 503 AA; 54481 MW; D04DB9128E0A7566 CRC64;
MRYDVVIAGA GPTGLMLACE LRLAGARTLV LERLAEPVDF SKALGVHART VELLDMRGLG
EGFQAEAPKL RGGNFASLGV PLDFSSFDTR HPYALFVPQV RTEELLTGRA LELGAELRRG
HAVTALEQDA DGVTVSVTGP EGPYEVECAY LVGCDGGGST VRKLLGIDFP GQDPHMFAVI
ADARFREELP HGEGMGPMRP YGVMRHDLRA WFAAFPLEPD VYRATVAFFD RPYADRRAPV
TEEDVRAALT EVAGSDFGMH DVRWLSRLTD TSRQAERYRD GRVLLAGDAC HIHLPAGGQG
LNLGFQDAVN LGWKLGATIA GTAPPELLDT YEAERRPIAA GVLRNTRAQA VLIDPDPRYE
GLRELMIELL HVPETNRYLA GLISALDVRY PMAGEHPLLG RRVPDLPLVT EDGTRQLSTY
FHAARGVLLT LGCDQPLADE AAAWKDRVDL VAAEGVADPG SAVDGLTALL VRPDGYICWT
AAPETGTDGL TDALRTWFGP PAM
