ROX_NOCFA
ID ROX_NOCFA Reviewed; 473 AA.
AC Q5YTV5;
DT 13-FEB-2019, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 03-AUG-2022, entry version 102.
DE RecName: Full=Rifampicin monooxygenase {ECO:0000303|PubMed:19942945};
DE Short=RIFMO {ECO:0000303|PubMed:19942945};
DE EC=1.14.13.- {ECO:0000303|PubMed:19942945};
GN Name=rox; OrderedLocusNames=NFA_35380;
OS Nocardia farcinica (strain IFM 10152).
OC Bacteria; Actinobacteria; Corynebacteriales; Nocardiaceae; Nocardia.
OX NCBI_TaxID=247156;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=IFM 10152;
RX PubMed=15466710; DOI=10.1073/pnas.0406410101;
RA Ishikawa J., Yamashita A., Mikami Y., Hoshino Y., Kurita H., Hotta K.,
RA Shiba T., Hattori M.;
RT "The complete genomic sequence of Nocardia farcinica IFM 10152.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:14925-14930(2004).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=19942945; DOI=10.1038/ja.2009.116;
RA Hoshino Y., Fujii S., Shinonaga H., Arai K., Saito F., Fukai T., Satoh H.,
RA Miyazaki Y., Ishikawa J.;
RT "Monooxygenation of rifampicin catalyzed by the rox gene product of
RT Nocardia farcinica: structure elucidation, gene identification and role in
RT drug resistance.";
RL J. Antibiot. 63:23-28(2010).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH FAD, SUBUNIT, AND
RP COFACTOR.
RX PubMed=27557658; DOI=10.1074/jbc.m116.745315;
RA Liu L.K., Abdelwahab H., Martin Del Campo J.S., Mehra-Chaudhary R.,
RA Sobrado P., Tanner J.J.;
RT "The Structure of the Antibiotic Deactivating, N-hydroxylating Rifampicin
RT Monooxygenase.";
RL J. Biol. Chem. 291:21553-21562(2016).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS), AND COFACTOR.
RX PubMed=29578336; DOI=10.1021/acs.biochem.8b00190;
RA Liu L.K., Dai Y., Abdelwahab H., Sobrado P., Tanner J.J.;
RT "Structural Evidence for Rifampicin Monooxygenase Inactivating Rifampicin
RT by Cleaving Its Ansa-Bridge.";
RL Biochemistry 57:2065-2068(2018).
CC -!- FUNCTION: Monooxygenase that can modify rifampicin, thereby
CC inactivating its antibiotic activity. It constitutes a secondary
CC rifampicin resistance factor. {ECO:0000269|PubMed:19942945}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADPH + O2 + rifampicin = H(+) + H2O + NADP(+) + rifampicin
CC para-naphthoquinone carboxamide; Xref=Rhea:RHEA:58696,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:71365,
CC ChEBI:CHEBI:142731; Evidence={ECO:0000269|PubMed:19942945};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58697;
CC Evidence={ECO:0000303|PubMed:15466710};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADH + O2 + rifampicin = H(+) + H2O + NAD(+) + rifampicin
CC para-naphthoquinone carboxamide; Xref=Rhea:RHEA:58712,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:71365,
CC ChEBI:CHEBI:142731; Evidence={ECO:0000269|PubMed:19942945};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58713;
CC Evidence={ECO:0000303|PubMed:19942945};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:27557658, ECO:0000269|PubMed:29578336};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:27557658}.
CC -!- DISRUPTION PHENOTYPE: No visible effect on rifampicin resistance.
CC {ECO:0000269|PubMed:19942945}.
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DR EMBL; AP006618; BAD58386.1; -; Genomic_DNA.
DR RefSeq; WP_011210071.1; NG_052045.1.
DR PDB; 5KOW; X-ray; 2.10 A; A=1-473.
DR PDB; 5KOX; X-ray; 1.80 A; A=1-473.
DR PDB; 6C7S; X-ray; 2.10 A; A=1-473.
DR PDBsum; 5KOW; -.
DR PDBsum; 5KOX; -.
DR PDBsum; 6C7S; -.
DR AlphaFoldDB; Q5YTV5; -.
DR SMR; Q5YTV5; -.
DR STRING; 247156.NFA_35380; -.
DR EnsemblBacteria; BAD58386; BAD58386; NFA_35380.
DR GeneID; 61134239; -.
DR KEGG; nfa:NFA_35380; -.
DR eggNOG; COG0654; Bacteria.
DR HOGENOM; CLU_009665_20_1_11; -.
DR OMA; DTAHPYG; -.
DR BRENDA; 1.14.13.211; 10091.
DR Proteomes; UP000006820; Chromosome.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; 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; FAD; Flavoprotein; Monooxygenase; Nucleotide-binding;
KW Oxidoreductase; Reference proteome.
FT CHAIN 1..473
FT /note="Rifampicin monooxygenase"
FT /id="PRO_0000446368"
FT BINDING 11..12
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:27557658,
FT ECO:0000269|PubMed:29578336"
FT BINDING 31..32
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:27557658,
FT ECO:0000269|PubMed:29578336"
FT BINDING 41..43
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:27557658,
FT ECO:0000269|PubMed:29578336"
FT BINDING 98
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:27557658,
FT ECO:0000269|PubMed:29578336"
FT BINDING 122
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:27557658,
FT ECO:0000269|PubMed:29578336"
FT BINDING 156
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:27557658,
FT ECO:0000269|PubMed:29578336"
FT BINDING 276
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:27557658,
FT ECO:0000269|PubMed:29578336"
FT BINDING 283..290
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:27557658,
FT ECO:0000269|PubMed:29578336"
FT STRAND 2..7
FT /evidence="ECO:0007829|PDB:5KOX"
FT HELIX 11..21
FT /evidence="ECO:0007829|PDB:5KOX"
FT TURN 22..24
FT /evidence="ECO:0007829|PDB:5KOX"
FT STRAND 27..32
FT /evidence="ECO:0007829|PDB:5KOX"
FT HELIX 47..55
FT /evidence="ECO:0007829|PDB:5KOX"
FT HELIX 59..63
FT /evidence="ECO:0007829|PDB:5KOX"
FT STRAND 66..69
FT /evidence="ECO:0007829|PDB:5KOX"
FT TURN 74..77
FT /evidence="ECO:0007829|PDB:5KOX"
FT STRAND 87..89
FT /evidence="ECO:0007829|PDB:5KOX"
FT STRAND 92..95
FT /evidence="ECO:0007829|PDB:5KOX"
FT HELIX 98..111
FT /evidence="ECO:0007829|PDB:5KOX"
FT STRAND 115..118
FT /evidence="ECO:0007829|PDB:5KOX"
FT STRAND 122..127
FT /evidence="ECO:0007829|PDB:5KOX"
FT STRAND 132..136
FT /evidence="ECO:0007829|PDB:5KOX"
FT STRAND 141..149
FT /evidence="ECO:0007829|PDB:5KOX"
FT HELIX 156..161
FT /evidence="ECO:0007829|PDB:5KOX"
FT STRAND 173..180
FT /evidence="ECO:0007829|PDB:5KOX"
FT HELIX 185..195
FT /evidence="ECO:0007829|PDB:5KOX"
FT TURN 196..198
FT /evidence="ECO:0007829|PDB:5KOX"
FT STRAND 203..206
FT /evidence="ECO:0007829|PDB:5KOX"
FT STRAND 208..210
FT /evidence="ECO:0007829|PDB:5KOX"
FT STRAND 212..217
FT /evidence="ECO:0007829|PDB:5KOX"
FT HELIX 230..241
FT /evidence="ECO:0007829|PDB:5KOX"
FT STRAND 248..257
FT /evidence="ECO:0007829|PDB:5KOX"
FT STRAND 260..262
FT /evidence="ECO:0007829|PDB:5KOX"
FT STRAND 266..268
FT /evidence="ECO:0007829|PDB:5KOX"
FT STRAND 271..273
FT /evidence="ECO:0007829|PDB:5KOX"
FT HELIX 275..277
FT /evidence="ECO:0007829|PDB:5KOX"
FT TURN 283..285
FT /evidence="ECO:0007829|PDB:5KOW"
FT HELIX 288..307
FT /evidence="ECO:0007829|PDB:5KOX"
FT TURN 313..316
FT /evidence="ECO:0007829|PDB:5KOX"
FT HELIX 317..340
FT /evidence="ECO:0007829|PDB:5KOX"
FT HELIX 345..358
FT /evidence="ECO:0007829|PDB:5KOX"
FT HELIX 361..371
FT /evidence="ECO:0007829|PDB:5KOX"
FT TURN 372..375
FT /evidence="ECO:0007829|PDB:5KOX"
FT TURN 385..388
FT /evidence="ECO:0007829|PDB:5KOX"
FT STRAND 397..400
FT /evidence="ECO:0007829|PDB:5KOX"
FT HELIX 401..404
FT /evidence="ECO:0007829|PDB:5KOX"
FT STRAND 410..414
FT /evidence="ECO:0007829|PDB:5KOX"
FT TURN 425..427
FT /evidence="ECO:0007829|PDB:5KOX"
FT STRAND 428..432
FT /evidence="ECO:0007829|PDB:5KOX"
FT STRAND 439..445
FT /evidence="ECO:0007829|PDB:5KOX"
FT STRAND 449..454
FT /evidence="ECO:0007829|PDB:5KOX"
FT HELIX 458..469
FT /evidence="ECO:0007829|PDB:5KOX"
SQ SEQUENCE 473 AA; 51364 MW; DBC19CD1A8AA2806 CRC64;
MIDVIIAGGG PTGLMLAGEL RLHGVRTVVL EKEPTPNQHS RSRGLHARSI EVMDQRGLLE
RFLAHGEQFR VGGFFAGLAA EWPADLDTAH SYVLAIPQVV TERLLTEHAT ELGAEIRRGC
EVAGLDQDAD GVTAELADGT RLRARYLVGC DGGRSTVRRL LGVDFPGEPT RVETLLADVR
IDVPVETLTA VVAEVRKTQL RFGAVPAGDG FFRLIVPAQG LSADRAAPTL DELKRCLHAT
AGTDFGVHSP RWLSRFGDAT RLAERYRTGR VLLAGDAAHI HPPTGGQGLN LGIQDAFNLG
WKLAAAIGGW APPDLLDSYH DERHPVAAEV LDNTRAQMTL LSLDPGPRAV RRLMAELVEF
PDVNRHLIEK ITAIAVRYDL GDGHDLVGRR LRDIPLTEGR LYERMRGGRG LLLDRTGRLS
VSGWSDRVDH LADPGAALDV PAALLRPDGH VAWVGEDQDD LLAHLPRWFG AAT
