TET55_UNKP
ID TET55_UNKP Reviewed; 385 AA.
AC A0A0H4TXY1;
DT 13-NOV-2019, integrated into UniProtKB/Swiss-Prot.
DT 14-OCT-2015, sequence version 1.
DT 03-AUG-2022, entry version 24.
DE RecName: Full=Flavin-dependent monooxygenase {ECO:0000305};
DE AltName: Full=Tetracycline destructase Tet(55) {ECO:0000303|PubMed:26097034};
DE Short=Tet(55);
DE EC=1.14.13.- {ECO:0000269|PubMed:28481346};
GN Name=tet(55) {ECO:0000303|PubMed:26097034};
OS Unknown prokaryotic organism.
OC Bacteria; environmental samples.
OX NCBI_TaxID=2725;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION IN INACTIVATING TETRACYCLINE,
RP AND ANTIBIOTIC RESISTANCE.
RX PubMed=26097034; DOI=10.1016/j.chembiol.2015.05.017;
RA Forsberg K.J., Patel S., Wencewicz T.A., Dantas G.;
RT "The Tetracycline Destructases: A Novel Family of Tetracycline-Inactivating
RT Enzymes.";
RL Chem. Biol. 22:888-897(2015).
RN [2] {ECO:0007744|PDB:5TUL}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS), FUNCTION, SUBSTRATE SPECIFICITY,
RP ACTIVITY REGULATION, DOMAIN, AND ANTIBIOTIC RESISTANCE.
RX PubMed=28481346; DOI=10.1038/nchembio.2376;
RA Park J., Gasparrini A.J., Reck M.R., Symister C.T., Elliott J.L.,
RA Vogel J.P., Wencewicz T.A., Dantas G., Tolia N.H.;
RT "Plasticity, dynamics, and inhibition of emerging tetracycline resistance
RT enzymes.";
RL Nat. Chem. Biol. 13:730-736(2017).
CC -!- FUNCTION: An FAD-requiring monooxygenase active on tetracycline
CC antibiotic and some of its derivatives, which leads to their
CC inactivation (PubMed:26097034). Expression in E.coli confers high
CC resistance to oxytetracycline, slightly less resistance to
CC tetracycline, moderate resistance to minocycline but no resistance to
CC tigecycline. Degrades tetracycline and oxytetracycline; the reaction
CC requires NADPH (PubMed:26097034). Degrades and confers resistance to
CC chlortetracycline (PubMed:28481346). {ECO:0000269|PubMed:26097034,
CC ECO:0000269|PubMed:28481346}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=7-chlorotetracycline + H(+) + NADPH + O2 = (1S,10S,10aS)-3-
CC (CONH2)-9-Cl-1-(Me2N)-3,3a,4,10-(HO)4-10-Me-2,5-dioxo-
CC 1H,10aH,11H,11aH-cyclopenta[b]anthracen-6-olate + CO + H2O + NADP(+);
CC Xref=Rhea:RHEA:61456, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17245, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:133598, ChEBI:CHEBI:144647;
CC Evidence={ECO:0000269|PubMed:28481346};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a tetracycline + H(+) + NADPH + O2 = a (1S,10aS)-3-(CONH2)-1-
CC (Me2N)-3,3a,4,6-(HO)4-2,5-dioxo-1H,10aH,11H,11aH-
CC cyclopenta[b]anthracene + CO + H2O + NADP(+); Xref=Rhea:RHEA:61564,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:17245, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:144644, ChEBI:CHEBI:144803;
CC Evidence={ECO:0000305|PubMed:26097034, ECO:0000305|PubMed:28481346};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000305|PubMed:28481346};
CC Note=Binds 1 FAD per subunit. {ECO:0000305|PubMed:28481346};
CC -!- ACTIVITY REGULATION: Inhibited by anhydrotetracycline.
CC {ECO:0000269|PubMed:28481346}.
CC -!- DOMAIN: Consists of an N-terminal FAD-binding domain with a Rossman
CC fold, a substrate-binding domain and a C-terminal helix that bridges
CC the 2 domains close to the antibiotic-binding site. This last helix is
CC flexible, is not found in TetX of Bacteroides species, and may
CC contribute to their different substrate specificities.
CC {ECO:0000269|PubMed:28481346}.
CC -!- MISCELLANEOUS: Isolated from an agricultural soil sample.
CC {ECO:0000305|PubMed:26097034}.
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.
CC {ECO:0000305}.
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DR EMBL; KR857689; AKQ05899.1; -; Genomic_DNA.
DR PDB; 5TUL; X-ray; 2.00 A; A=1-385.
DR PDBsum; 5TUL; -.
DR AlphaFoldDB; A0A0H4TXY1; -.
DR SMR; A0A0H4TXY1; -.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR Gene3D; 3.50.50.60; -; 1.
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 resistance; FAD; Flavoprotein; NADP;
KW Nucleotide-binding; Oxidoreductase.
FT CHAIN 1..385
FT /note="Flavin-dependent monooxygenase"
FT /id="PRO_0000448492"
FT BINDING 12..15
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A0A059WYP6"
FT BINDING 34..36
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A0A059WYP6"
FT BINDING 44..47
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A0A059WYP6"
FT BINDING 105
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A0A059WYP6"
FT BINDING 267
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A0A059WYP6"
FT BINDING 289
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A0A059WYP6"
FT BINDING 296..302
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A0A059WYP6"
FT STRAND 6..10
FT /evidence="ECO:0007829|PDB:5TUL"
FT HELIX 15..25
FT /evidence="ECO:0007829|PDB:5TUL"
FT STRAND 29..33
FT /evidence="ECO:0007829|PDB:5TUL"
FT STRAND 35..38
FT /evidence="ECO:0007829|PDB:5TUL"
FT STRAND 45..48
FT /evidence="ECO:0007829|PDB:5TUL"
FT HELIX 51..58
FT /evidence="ECO:0007829|PDB:5TUL"
FT HELIX 62..67
FT /evidence="ECO:0007829|PDB:5TUL"
FT STRAND 74..78
FT /evidence="ECO:0007829|PDB:5TUL"
FT STRAND 84..88
FT /evidence="ECO:0007829|PDB:5TUL"
FT STRAND 101..104
FT /evidence="ECO:0007829|PDB:5TUL"
FT HELIX 105..115
FT /evidence="ECO:0007829|PDB:5TUL"
FT TURN 116..118
FT /evidence="ECO:0007829|PDB:5TUL"
FT STRAND 121..124
FT /evidence="ECO:0007829|PDB:5TUL"
FT STRAND 127..132
FT /evidence="ECO:0007829|PDB:5TUL"
FT STRAND 137..141
FT /evidence="ECO:0007829|PDB:5TUL"
FT STRAND 146..154
FT /evidence="ECO:0007829|PDB:5TUL"
FT HELIX 161..166
FT /evidence="ECO:0007829|PDB:5TUL"
FT TURN 169..171
FT /evidence="ECO:0007829|PDB:5TUL"
FT STRAND 172..187
FT /evidence="ECO:0007829|PDB:5TUL"
FT STRAND 193..201
FT /evidence="ECO:0007829|PDB:5TUL"
FT STRAND 204..210
FT /evidence="ECO:0007829|PDB:5TUL"
FT STRAND 216..224
FT /evidence="ECO:0007829|PDB:5TUL"
FT HELIX 235..246
FT /evidence="ECO:0007829|PDB:5TUL"
FT HELIX 253..259
FT /evidence="ECO:0007829|PDB:5TUL"
FT HELIX 260..262
FT /evidence="ECO:0007829|PDB:5TUL"
FT STRAND 267..277
FT /evidence="ECO:0007829|PDB:5TUL"
FT STRAND 279..281
FT /evidence="ECO:0007829|PDB:5TUL"
FT STRAND 284..286
FT /evidence="ECO:0007829|PDB:5TUL"
FT HELIX 289..292
FT /evidence="ECO:0007829|PDB:5TUL"
FT TURN 296..298
FT /evidence="ECO:0007829|PDB:5TUL"
FT HELIX 301..318
FT /evidence="ECO:0007829|PDB:5TUL"
FT STRAND 319..321
FT /evidence="ECO:0007829|PDB:5TUL"
FT HELIX 322..350
FT /evidence="ECO:0007829|PDB:5TUL"
FT HELIX 359..377
FT /evidence="ECO:0007829|PDB:5TUL"
SQ SEQUENCE 385 AA; 42982 MW; DDEBA71AF97E5004 CRC64;
MPHTKKILVI GASIAGPALC YWLNHYGFQP TLVEKNQSTR KGGYAIDLRG IAVDVAKQMG
IYDSVCAMRT SLQCVRYVDA AGNLLFEEHG EKGGFRQGDE VEIVRGDLVD ILMKTITDIP
CFYDHAIESL TQHDDHVTVQ FKNGKTENYD LVIAADGLHS ATRRMVFSKD DYHLRNLGCY
ISVFSIPNYL QLDHCETLLE AKQKLVSITS DKDSTKAFAG FMFRSSNSPN YIRDEASQKD
FLRENFTNHG WESNKLLSLM NDANDFYFDA IMQVKMKDWT KGRIALVGDA GYTPSPLSGQ
GTSLALVGAY ILAGELKTAT DHVAAFARYN ELLKPYVEAN QAFGVWVSES FLADEPLSAE
QAEERNNIVL GIMKKATHAI ELPEY
