TET56_LEGLN
ID TET56_LEGLN Reviewed; 389 AA.
AC D3HKY4;
DT 13-NOV-2019, integrated into UniProtKB/Swiss-Prot.
DT 23-MAR-2010, sequence version 1.
DT 03-AUG-2022, entry version 72.
DE RecName: Full=Flavin-dependent monooxygenase {ECO:0000305};
DE AltName: Full=Tetracycline destructase Tet(56) {ECO:0000303|PubMed:26097034};
DE Short=Tet(56);
DE EC=1.14.13.- {ECO:0000305|PubMed:26097034};
GN Name=tet(56); OrderedLocusNames=LLO_2673;
OS Legionella longbeachae serogroup 1 (strain NSW150).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales;
OC Legionellaceae; Legionella.
OX NCBI_TaxID=661367;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NSW150;
RX PubMed=20174605; DOI=10.1371/journal.pgen.1000851;
RA Cazalet C., Gomez-Valero L., Rusniok C., Lomma M., Dervins-Ravault D.,
RA Newton H.J., Sansom F.M., Jarraud S., Zidane N., Ma L., Bouchier C.,
RA Etienne J., Hartland E.L., Buchrieser C.;
RT "Analysis of the Legionella longbeachae genome and transcriptome uncovers
RT unique strategies to cause Legionnaires' disease.";
RL PLoS Genet. 6:E1000851-E1000851(2010).
RN [2]
RP FUNCTION IN INACTIVATING TETRACYCLINE, 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 [3] {ECO:0007744|PDB:5TUM}
RP X-RAY CRYSTALLOGRAPHY (3.30 ANGSTROMS) IN COMPLEX WITH FAD, FUNCTION,
RP SUBSTRATE SPECIFICITY, COFACTOR, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, DOMAIN, DISRUPTION PHENOTYPE, 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 tetracycline and oxytetracycline, does not confer
CC resistance to minocycline or tigecycline. The reaction requires NADPH
CC (PubMed:26097034). Expression in L.pneumophila confers resistance to
CC tetracycline (PubMed:28481346). Degrades and confers resistance to
CC tetracycline and chlortetracycline (PubMed:26097034, PubMed:28481346).
CC {ECO:0000269|PubMed:26097034, 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 -!- 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:0000305|PubMed:28481346};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:28481346};
CC Note=Binds 1 FAD per subunit. {ECO:0000269|PubMed:28481346};
CC -!- ACTIVITY REGULATION: Inhibited by anhydrotetracycline.
CC {ECO:0000269|PubMed:28481346}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=7.7 uM for tetracycline {ECO:0000269|PubMed:28481346};
CC KM=3.7 uM for chlortetracycline {ECO:0000269|PubMed:28481346};
CC Note=kcat for tetracycline is 6.4 min(-1), kcat for chlortetracycline
CC is 6.6 min(-1). {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 -!- DISRUPTION PHENOTYPE: Increase in bacterial tetracycline sensitivity.
CC {ECO:0000269|PubMed:28481346}.
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; FN650140; CBJ13102.1; -; Genomic_DNA.
DR RefSeq; WP_003635403.1; NC_013861.1.
DR PDB; 5TUM; X-ray; 3.30 A; A/B=1-389.
DR PDBsum; 5TUM; -.
DR AlphaFoldDB; D3HKY4; -.
DR SMR; D3HKY4; -.
DR STRING; 661367.LLO_2673; -.
DR EnsemblBacteria; CBJ13102; CBJ13102; LLO_2673.
DR KEGG; llo:LLO_2673; -.
DR eggNOG; COG0654; Bacteria.
DR HOGENOM; CLU_009665_1_0_6; -.
DR OMA; MDLTIAY; -.
DR OrthoDB; 504558at2; -.
DR Proteomes; UP000001060; Chromosome.
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..389
FT /note="Flavin-dependent monooxygenase"
FT /id="PRO_0000448493"
FT BINDING 12..15
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0007744|PDB:5TUM"
FT BINDING 34..35
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0007744|PDB:5TUM"
FT BINDING 44
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0007744|PDB:5TUM"
FT BINDING 105
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0007744|PDB:5TUM"
FT BINDING 267
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0007744|PDB:5TUM"
FT BINDING 289
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0007744|PDB:5TUM"
FT STRAND 7..11
FT /evidence="ECO:0007829|PDB:5TUM"
FT HELIX 15..25
FT /evidence="ECO:0007829|PDB:5TUM"
FT STRAND 31..33
FT /evidence="ECO:0007829|PDB:5TUM"
FT STRAND 35..38
FT /evidence="ECO:0007829|PDB:5TUM"
FT STRAND 45..48
FT /evidence="ECO:0007829|PDB:5TUM"
FT HELIX 52..58
FT /evidence="ECO:0007829|PDB:5TUM"
FT HELIX 62..68
FT /evidence="ECO:0007829|PDB:5TUM"
FT STRAND 74..78
FT /evidence="ECO:0007829|PDB:5TUM"
FT STRAND 84..88
FT /evidence="ECO:0007829|PDB:5TUM"
FT STRAND 101..104
FT /evidence="ECO:0007829|PDB:5TUM"
FT HELIX 105..115
FT /evidence="ECO:0007829|PDB:5TUM"
FT STRAND 127..132
FT /evidence="ECO:0007829|PDB:5TUM"
FT STRAND 137..141
FT /evidence="ECO:0007829|PDB:5TUM"
FT STRAND 146..154
FT /evidence="ECO:0007829|PDB:5TUM"
FT HELIX 161..166
FT /evidence="ECO:0007829|PDB:5TUM"
FT TURN 169..171
FT /evidence="ECO:0007829|PDB:5TUM"
FT STRAND 172..187
FT /evidence="ECO:0007829|PDB:5TUM"
FT STRAND 193..201
FT /evidence="ECO:0007829|PDB:5TUM"
FT STRAND 204..210
FT /evidence="ECO:0007829|PDB:5TUM"
FT STRAND 212..223
FT /evidence="ECO:0007829|PDB:5TUM"
FT HELIX 235..246
FT /evidence="ECO:0007829|PDB:5TUM"
FT HELIX 253..258
FT /evidence="ECO:0007829|PDB:5TUM"
FT STRAND 267..277
FT /evidence="ECO:0007829|PDB:5TUM"
FT STRAND 279..281
FT /evidence="ECO:0007829|PDB:5TUM"
FT STRAND 284..286
FT /evidence="ECO:0007829|PDB:5TUM"
FT HELIX 289..292
FT /evidence="ECO:0007829|PDB:5TUM"
FT HELIX 296..298
FT /evidence="ECO:0007829|PDB:5TUM"
FT HELIX 301..318
FT /evidence="ECO:0007829|PDB:5TUM"
FT TURN 319..321
FT /evidence="ECO:0007829|PDB:5TUM"
FT HELIX 323..351
FT /evidence="ECO:0007829|PDB:5TUM"
FT HELIX 365..368
FT /evidence="ECO:0007829|PDB:5TUM"
FT HELIX 369..378
FT /evidence="ECO:0007829|PDB:5TUM"
SQ SEQUENCE 389 AA; 44023 MW; C02E3F6B2B75D124 CRC64;
MSKNIKILVI GAGVAGPAVC YWLRRFGFSP VLIEKYASIR KGGQALDVRG IATHIAREMG
IYDQICEMRT RIERGRFVDS SGKVLHEEQG EKFGFRQDDE VEILRGDLVE ILMKTIADVP
CYFNQSIISI EQNADNVTVI FMDGRIEQYD LVIAADGIHS AIRRMIFEKN EYQLIHLGAY
LSTFTIPNYL GLSHIDLECE ANNKLVSINS DNNPEIARAG FMFRSQHLLN DIRDEQEQKQ
FLRDTFRDFG WETQNILNRM PESNDFYFDA ITQVKMNSWT KGRIALVGDA GYCPSPLSGQ
GNNLAFVGAY ILAGELKVAN GNYTRAFTRY NALLRSFVDA NQKFGVWVSE SFLVKDEVSK
EIAEERSNKI LAMIKSISNG ITLPQYESS
