RDXA_HELPY
ID RDXA_HELPY Reviewed; 210 AA.
AC O25608; O30585; Q9AHD6; Q9AHF7; Q9AHF8;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 99.
DE RecName: Full=Oxygen-insensitive NADPH nitroreductase;
DE EC=1.-.-.-;
GN Name=rdxA; OrderedLocusNames=HP_0954;
OS Helicobacter pylori (strain ATCC 700392 / 26695) (Campylobacter pylori).
OC Bacteria; Proteobacteria; Epsilonproteobacteria; Campylobacterales;
OC Helicobacteraceae; Helicobacter.
OX NCBI_TaxID=85962;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION AS A NITROREDUCTASE, AND EFFECT
RP ON METRONIDAZOLE RESISTANCE.
RC STRAIN=HP500;
RX PubMed=9622362; DOI=10.1046/j.1365-2958.1998.00806.x;
RA Goodwin A., Kersulyte D., Sisson G., Veldhuyzen van Zanten S.J.O.,
RA Berg D.E., Hoffman P.S.;
RT "Metronidazole resistance in Helicobacter pylori is due to null mutations
RT in a gene (rdxA) that encodes an oxygen-insensitive NADPH nitroreductase.";
RL Mol. Microbiol. 28:383-393(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS RESISTANT TO METRONIDAZOLE, AND
RP MUTAGENESIS OF CYS-19 AND THR-49.
RC STRAIN=69A, ATCC 43504 / NCTC 11637 / JCM 7653 / RPH 13487, and
RC ATCC 49503 / 60190;
RX PubMed=11181392; DOI=10.1128/aac.45.3.962-965.2001;
RA Paul R., Postius S., Melchers K., Schafer K.P.;
RT "Mutations of the Helicobacter pylori genes rdxA and pbp1 cause resistance
RT against metronidazole and amoxicillin.";
RL Antimicrob. Agents Chemother. 45:962-965(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700392 / 26695;
RX PubMed=9252185; DOI=10.1038/41483;
RA Tomb J.-F., White O., Kerlavage A.R., Clayton R.A., Sutton G.G.,
RA Fleischmann R.D., Ketchum K.A., Klenk H.-P., Gill S.R., Dougherty B.A.,
RA Nelson K.E., Quackenbush J., Zhou L., Kirkness E.F., Peterson S.N.,
RA Loftus B.J., Richardson D.L., Dodson R.J., Khalak H.G., Glodek A.,
RA McKenney K., FitzGerald L.M., Lee N., Adams M.D., Hickey E.K., Berg D.E.,
RA Gocayne J.D., Utterback T.R., Peterson J.D., Kelley J.M., Cotton M.D.,
RA Weidman J.F., Fujii C., Bowman C., Watthey L., Wallin E., Hayes W.S.,
RA Borodovsky M., Karp P.D., Smith H.O., Fraser C.M., Venter J.C.;
RT "The complete genome sequence of the gastric pathogen Helicobacter
RT pylori.";
RL Nature 388:539-547(1997).
RN [4]
RP INVOLVEMENT IN RESISTANCE TO METRONIDAZOLE.
RC STRAIN=ATCC 43504 / NCTC 11637 / JCM 7653 / RPH 13487;
RX PubMed=10543743; DOI=10.1128/aac.43.11.2657;
RA Debets-Ossenkopp Y.J., Pot R.G.J., van Westerloo D.J., Goodwin A.,
RA Vandenbroucke-Grauls C.M.J.E., Berg D.E., Hoffman P.S., Kusters J.G.;
RT "Insertion of mini-IS605 and deletion of adjacent sequences in the
RT nitroreductase (rdxA) gene cause metronidazole resistance in Helicobacter
RT pylori NCTC11637.";
RL Antimicrob. Agents Chemother. 43:2657-2662(1999).
CC -!- FUNCTION: Reduction of a variety of nitroaromatic compounds using NADPH
CC as source of reducing equivalents; two electrons are transferred (By
CC similarity). Capable of reducing metronidazole; inactive RdxA renders
CC the bacterium resistant to this compound. The reduction of
CC metronidazole generates hydroxylamine, a potent mutagen and
CC bactericide. {ECO:0000250, ECO:0000269|PubMed:9622362}.
CC -!- SIMILARITY: Belongs to the nitroreductase family. {ECO:0000305}.
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DR EMBL; AF012552; AAC46349.1; -; Genomic_DNA.
DR EMBL; AF315501; AAK17124.1; -; Genomic_DNA.
DR EMBL; AF315502; AAK17125.1; -; Genomic_DNA.
DR EMBL; AF316109; AAK19260.1; -; Genomic_DNA.
DR EMBL; AE000511; AAD07997.1; -; Genomic_DNA.
DR PIR; B64639; B64639.
DR RefSeq; NP_207746.1; NC_000915.1.
DR RefSeq; WP_000670110.1; NC_018939.1.
DR PDB; 3QDL; X-ray; 2.00 A; A/B/C/D=1-210.
DR PDBsum; 3QDL; -.
DR AlphaFoldDB; O25608; -.
DR SMR; O25608; -.
DR DIP; DIP-3602N; -.
DR IntAct; O25608; 2.
DR MINT; O25608; -.
DR STRING; 85962.C694_04915; -.
DR DrugBank; DB00916; Metronidazole.
DR PaxDb; O25608; -.
DR EnsemblBacteria; AAD07997; AAD07997; HP_0954.
DR KEGG; hpy:HP_0954; -.
DR PATRIC; fig|85962.47.peg.1022; -.
DR eggNOG; COG0778; Bacteria.
DR OMA; EQCYIAV; -.
DR PhylomeDB; O25608; -.
DR BioCyc; MetaCyc:HP_RS04670-MON; -.
DR Proteomes; UP000000429; Chromosome.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR CDD; cd02149; NfsB-like; 1.
DR Gene3D; 3.40.109.10; -; 1.
DR InterPro; IPR033878; NfsB-like.
DR InterPro; IPR029479; Nitroreductase.
DR InterPro; IPR000415; Nitroreductase-like.
DR Pfam; PF00881; Nitroreductase; 1.
DR SUPFAM; SSF55469; SSF55469; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic resistance; NADP; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..210
FT /note="Oxygen-insensitive NADPH nitroreductase"
FT /id="PRO_0000321864"
FT BINDING 150..155
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT VARIANT 14
FT /note="N -> K (in strain: ATCC 43504 / NCTC 11637 / JCM
FT 7653 / RPH 13487; resistant to metronidazole)"
FT VARIANT 31
FT /note="T -> E (in strain: HP500, 69A and ATCC 43504 / NCTC
FT 11637 / JCM 7653 / RPH 13487; resistant to metronidazole)"
FT VARIANT 36
FT /note="I -> V (in strain: ATCC 43504 / NCTC 11637 / JCM
FT 7653 / RPH 13487; resistant to metronidazole)"
FT VARIANT 53
FT /note="H -> R (in strain: ATCC 49503)"
FT VARIANT 56
FT /note="M -> I (in strain: ATCC 43504 / NCTC 11637 / JCM
FT 7653 / RPH 13487; resistant to metronidazole)"
FT VARIANT 59
FT /note="D -> N (in strain: HP500, 69A, ATCC 43504 / NCTC
FT 11637 / JCM 7653 / RPH 13487; resistant to metronidazole
FT and ATCC 49503 / 60190)"
FT VARIANT 63..93
FT /note="KKQIAAHSYFNEEMIKSASALMVVCSLRPSE -> NHPSRNPKH (in
FT strain: ATCC 43504 / NCTC 11637 / JCM 7653 / RPH 13487;
FT resistant to metronidazole)"
FT VARIANT 64
FT /note="K -> N (in strain: 69A)"
FT VARIANT 68
FT /note="A -> V (in strain: HP500)"
FT VARIANT 90
FT /note="R -> K (in strain: ATCC 49503 / 60190)"
FT VARIANT 97
FT /note="H -> T (in strain: 69A)"
FT VARIANT 98
FT /note="G -> S (in strain: ATCC 49503 / 60190)"
FT VARIANT 106
FT /note="P -> S (in strain: 69A)"
FT VARIANT 131
FT /note="R -> K (in strain: 69A)"
FT VARIANT 172
FT /note="V -> I (in strain: 69A)"
FT VARIANT 183
FT /note="A -> V (in strain: ATCC 49503 / 60190)"
FT MUTAGEN 19
FT /note="C->Y: Loss of function and acquisition of resistance
FT to metronidazole."
FT /evidence="ECO:0000269|PubMed:11181392"
FT MUTAGEN 49
FT /note="T->K: Loss of function and acquisition of resistance
FT to metronidazole."
FT /evidence="ECO:0000269|PubMed:11181392"
FT HELIX 6..15
FT /evidence="ECO:0007829|PDB:3QDL"
FT HELIX 30..41
FT /evidence="ECO:0007829|PDB:3QDL"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:3QDL"
FT STRAND 52..57
FT /evidence="ECO:0007829|PDB:3QDL"
FT HELIX 60..67
FT /evidence="ECO:0007829|PDB:3QDL"
FT HELIX 71..73
FT /evidence="ECO:0007829|PDB:3QDL"
FT HELIX 74..79
FT /evidence="ECO:0007829|PDB:3QDL"
FT STRAND 81..88
FT /evidence="ECO:0007829|PDB:3QDL"
FT HELIX 91..94
FT /evidence="ECO:0007829|PDB:3QDL"
FT HELIX 131..154
FT /evidence="ECO:0007829|PDB:3QDL"
FT STRAND 157..161
FT /evidence="ECO:0007829|PDB:3QDL"
FT HELIX 166..171
FT /evidence="ECO:0007829|PDB:3QDL"
FT TURN 172..176
FT /evidence="ECO:0007829|PDB:3QDL"
FT STRAND 181..189
FT /evidence="ECO:0007829|PDB:3QDL"
FT STRAND 191..193
FT /evidence="ECO:0007829|PDB:3QDL"
FT HELIX 203..206
FT /evidence="ECO:0007829|PDB:3QDL"
FT STRAND 207..210
FT /evidence="ECO:0007829|PDB:3QDL"
SQ SEQUENCE 210 AA; 24068 MW; DFF15D2D102C002C CRC64;
MKFLDQEKRR QLLNERHSCK MFDSHYEFSS TELEEIAEIA RLSPSSYNTQ PWHFVMVTDK
DLKKQIAAHS YFNEEMIKSA SALMVVCSLR PSELLPHGHY MQNLYPESYK VRVIPSFAQM
LGVRFNHSMQ RLESYILEQC YIAVGQICMG VSLMGLDSCI IGGFDPLKVG EVLEERINKP
KIACLIALGK RVAEASQKSR KSKVDAITWL
