TETX_BACFG
ID TETX_BACFG Reviewed; 388 AA.
AC Q01911;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1993, sequence version 1.
DT 03-AUG-2022, entry version 92.
DE RecName: Full=Flavin-dependent monooxygenase {ECO:0000255|HAMAP-Rule:MF_00845};
DE AltName: Full=TetX monooxygenase {ECO:0000255|HAMAP-Rule:MF_00845};
DE Short=TetX {ECO:0000255|HAMAP-Rule:MF_00845};
DE EC=1.14.13.231 {ECO:0000255|HAMAP-Rule:MF_00845, ECO:0000305|PubMed:2644186};
DE AltName: Full=Tetracycline resistance protein from transposon Tn4351/Tn4400 {ECO:0000303|PubMed:1846135};
GN Name=tetX {ECO:0000303|PubMed:2644186};
GN Synonyms=Tcr* {ECO:0000303|PubMed:2644186};
OS Bacteroides fragilis.
OC Bacteria; Bacteroidetes; Bacteroidia; Bacteroidales; Bacteroidaceae;
OC Bacteroides.
OX NCBI_TaxID=817;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND SUBCELLULAR LOCATION.
RC TRANSPOSON=Tn4351, and Tn4400;
RX PubMed=1846135; DOI=10.1128/jb.173.1.176-183.1991;
RA Speer B.S., Bedzyk L., Salyers A.A.;
RT "Evidence that a novel tetracycline resistance gene found on two
RT Bacteroides transposons encodes an NADP-requiring oxidoreductase.";
RL J. Bacteriol. 173:176-183(1991).
RN [2]
RP IDENTIFICATION.
RC STRAIN=479-l / 92;
RX PubMed=6379711; DOI=10.1016/0147-619x(84)90031-3;
RA Guiney D.G. Jr., Hasegawa P., Davis C.E.;
RT "Expression in Escherichia coli of cryptic tetracycline resistance genes
RT from bacteroides R plasmids.";
RL Plasmid 11:248-252(1984).
RN [3]
RP FUNCTION IN INACTIVATING TETRACYCLINE.
RC STRAIN=479-l / 92;
RX PubMed=2644186; DOI=10.1128/jb.171.1.148-153.1989;
RA Speer B.S., Salyers A.A.;
RT "Novel aerobic tetracycline resistance gene that chemically modifies
RT tetracycline.";
RL J. Bacteriol. 171:148-153(1989).
CC -!- FUNCTION: An FAD-requiring monooxygenase active on some tetracycline
CC antibiotic derivatives, which leads to their inactivation. Hydroxylates
CC carbon 11a of tetracycline and some analogs. {ECO:0000255|HAMAP-
CC Rule:MF_00845}.
CC -!- FUNCTION: Confers resistance to tetracycline via an oxidoreductase
CC activity; NADPH is more active than NAD (Probable). Expression in
CC E.coli leads to breakdown of tetracycline. Confers resistance to
CC doxycycline, chlortetracycline, oxytetracycline and minocycline
CC (PubMed:2644186). {ECO:0000269|PubMed:2644186,
CC ECO:0000305|PubMed:1846135}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a tetracycline + H(+) + NADPH + O2 = an 11a-
CC hydroxytetracycline + H2O + NADP(+); Xref=Rhea:RHEA:61444,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:144644,
CC ChEBI:CHEBI:144645; Evidence={ECO:0000255|HAMAP-Rule:MF_00845,
CC ECO:0000305|PubMed:2644186};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + NADPH + O2 + tetracycline = 11a-hydroxytetracycline +
CC H2O + NADP(+); Xref=Rhea:RHEA:50004, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:77932, ChEBI:CHEBI:132727;
CC EC=1.14.13.231; Evidence={ECO:0000305|PubMed:2644186};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + NADPH + O2 + oxytetracycline = 11a-hydroxy-
CC oxytetracycline + H2O + NADP(+); Xref=Rhea:RHEA:61452,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:133011,
CC ChEBI:CHEBI:144646; Evidence={ECO:0000305|PubMed:2644186};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00845};
CC -!- SUBUNIT: Monomer. {ECO:0000255|HAMAP-Rule:MF_00845}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00845,
CC ECO:0000305|PubMed:1846135}.
CC -!- DOMAIN: Consists of an N-terminal FAD-binding domain with a Rossman
CC fold and a C-terminal substrate-binding domain. {ECO:0000255|HAMAP-
CC Rule:MF_00845}.
CC -!- MISCELLANEOUS: Activity is not seen in B.fragilis, an anaerobic
CC bacterium. Activity is seen when expressed in aerobically growing
CC E.coli. {ECO:0000269|PubMed:6379711}.
CC -!- MISCELLANEOUS: Tetracycline antibiotics bind to the ribosomal acceptor
CC site (A-site), preventing binding of the aminoacyl-tRNA to the A-site.
CC The hydrophilic side of tetracycline makes many hydrogen-bonding
CC interactions with oxygen atoms of the ribosome's phosphate backbone.
CC {ECO:0000250|UniProtKB:Q93L51}.
CC -!- SIMILARITY: Belongs to the aromatic-ring hydroxylase family. TetX
CC subfamily. {ECO:0000255|HAMAP-Rule:MF_00845}.
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DR EMBL; M37699; AAA27471.1; -; Genomic_DNA.
DR PIR; A39191; A39191.
DR RefSeq; WP_063856436.1; NG_048304.1.
DR AlphaFoldDB; Q01911; -.
DR SMR; Q01911; -.
DR KEGG; ag:AAA27471; -.
DR BioCyc; MetaCyc:MON-19928; -.
DR BRENDA; 1.14.13.231; 755.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR Gene3D; 3.50.50.60; -; 1.
DR HAMAP; MF_00845; TetX_monooxygenase; 1.
DR InterPro; IPR002938; FAD-bd.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR043683; TetX_monooxygenase.
DR Pfam; PF01494; FAD_binding_3; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW Antibiotic resistance; Cytoplasm; FAD; Flavoprotein; Monooxygenase; NADP;
KW Nucleotide-binding; Oxidoreductase; Transposable element.
FT CHAIN 1..388
FT /note="Flavin-dependent monooxygenase"
FT /id="PRO_0000072488"
FT BINDING 54
FT /ligand="NADPH"
FT /ligand_id="ChEBI:CHEBI:57783"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00845"
FT BINDING 61
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00845"
FT BINDING 117
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00845"
FT BINDING 311
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00845"
SQ SEQUENCE 388 AA; 43725 MW; 16209EA7CC5A11D2 CRC64;
MTMRIDTDKQ MNLLSDKNVA IIGGGPVGLT MAKLLQQNGI DVSVYERDND REARIFGGTL
DLHKGSGQEA MKKAGLLQTY YDLALPMGVN IADKKGNILS TKNVKPENRF DNPEINRNDL
RAILLNSLEN DTVIWDRKLV MLEPGKKKWT LTFENKPSET ADLVILANGG MSKVRKFVTD
TEVEETGTFN IQADIHQPEI NCPGFFQLCN GNRLMASHQG NLLFANPNNN GALHFGISFK
TPDEWKNQTQ VDFQNRNSVV DFLLKEFSDW DERYKELIHT TLSFVGLATR IFPLEKPWKS
KRPLPITMIG DAAHLMPPFA GQGVNSGLVD ALILSDNLAD GKFNSIEEAV KNYEQQMFMY
GKEAQEESTQ NEIEMFKPDF TFQQLLNV
