O25608 (RDXA_HELPY) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Oxygen-insensitive NADPH nitroreductase
EC=1.-.-.-

Gene names

Name:	rdxA
Ordered Locus Names:	HP_0954

Organism

Helicobacter pylori (strain ATCC 700392 / 26695) (Campylobacter pylori)

Taxonomic identifier

85962 [NCBI]

Taxonomic lineage

Bacteria › Proteobacteria › Epsilonproteobacteria › Campylobacterales › Helicobacteraceae › Helicobacter

Protein attributes

Sequence length	210 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Reduction of a variety of nitroaromatic compounds using NADPH as source of reducing equivalents; two electrons are transferred By similarity. Capable of reducing metronidazole; inactive rdxA renders the bacterium resistant to this compound. The reduction of metronidazole generates hydroxylamine, a potent mutagen and bactericide. Ref.1
Catalytic activity	A 5,6,7,8-tetrahydropteridine + NAD(P)+ = a 6,7-dihydropteridine + NAD(P)H.
Sequence similarities	Belongs to the nitroreductase family.

Ontologies

Keywords
Biological process	Antibiotic resistance
Ligand	NADP
Molecular function	Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	response to antibiotic Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	oxidoreductase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 210	210	Oxygen-insensitive NADPH nitroreductase		PRO_0000321864
Regions
	Nucleotide binding	150 – 155	6	NADP By similarity
Natural variations
	Natural variant	14	1	N → K in strain: ATCC 43504 / NCTC 11637 / JCM 7653 / RPH 13487; resistant to metronidazole.
	Natural variant	31	1	T → E in strain: HP500, 69A and ATCC 43504 / NCTC 11637 / JCM 7653 / RPH 13487; resistant to metronidazole.
	Natural variant	36	1	I → V in strain: ATCC 43504 / NCTC 11637 / JCM 7653 / RPH 13487; resistant to metronidazole.
	Natural variant	53	1	H → R in strain: ATCC 49503.
	Natural variant	56	1	M → I in strain: ATCC 43504 / NCTC 11637 / JCM 7653 / RPH 13487; resistant to metronidazole.
	Natural variant	59	1	D → N in strain: HP500, 69A, ATCC 43504 / NCTC 11637 / JCM 7653 / RPH 13487; resistant to metronidazole and ATCC 49503 / 60190.
	Natural variant	63 – 93	31	KKQIA…LRPSE → NHPSRNPKH in strain: ATCC 43504 / NCTC 11637 / JCM 7653 / RPH 13487; resistant to metronidazole.
	Natural variant	64	1	K → N in strain: 69A.
	Natural variant	68	1	A → V in strain: HP500.
	Natural variant	90	1	R → K in strain: ATCC 49503 / 60190.
	Natural variant	97	1	H → T in strain: 69A.
	Natural variant	98	1	G → S in strain: ATCC 49503 / 60190.
	Natural variant	106	1	P → S in strain: 69A.
	Natural variant	131	1	R → K in strain: 69A.
	Natural variant	172	1	V → I in strain: 69A.
	Natural variant	183	1	A → V in strain: ATCC 49503 / 60190.
Experimental info
	Mutagenesis	19	1	C → Y: Loss of function and acquisition of resistance to metronidazole. Ref.2
	Mutagenesis	49	1	T → K: Loss of function and acquisition of resistance to metronidazole. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	O25608 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: DFF15D2D102C002C	FASTA	210	24,068
	10 20 30 40 50 60 MKFLDQEKRR QLLNERHSCK MFDSHYEFSS TELEEIAEIA RLSPSSYNTQ PWHFVMVTDK 70 80 90 100 110 120 DLKKQIAAHS YFNEEMIKSA SALMVVCSLR PSELLPHGHY MQNLYPESYK VRVIPSFAQM 130 140 150 160 170 180 LGVRFNHSMQ RLESYILEQC YIAVGQICMG VSLMGLDSCI IGGFDPLKVG EVLEERINKP 190 200 210 KIACLIALGK RVAEASQKSR KSKVDAITWL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Metronidazole resistance in Helicobacter pylori is due to null mutations in a gene (rdxA) that encodes an oxygen-insensitive NADPH nitroreductase." Goodwin A., Kersulyte D., Sisson G., Veldhuyzen van Zanten S.J.O., Berg D.E., Hoffman P.S. Mol. Microbiol. 28:383-393(1998) [PubMed: 9622362] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION AS A NITROREDUCTASE, ABSENCE OF FLAVIN COFACTOR, EFFECT ON METRONIDAZOLE RESISTANCE. Strain: HP500.
[2]	"Mutations of the Helicobacter pylori genes rdxA and pbp1 cause resistance against metronidazole and amoxicillin." Paul R., Postius S., Melchers K., Schafer K.P. Antimicrob. Agents Chemother. 45:962-965(2001) [PubMed: 11181392] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS RESISTANT TO METRONIDAZOLE, MUTAGENESIS OF CYS-19 AND THR-49. Strain: 69A, ATCC 43504 / NCTC 11637 / JCM 7653 / RPH 13487 and ATCC 49503 / 60190.
[3]	"The complete genome sequence of the gastric pathogen Helicobacter pylori." Tomb J.-F., White O., Kerlavage A.R., Clayton R.A., Sutton G.G., Fleischmann R.D., Ketchum K.A., Klenk H.-P., Gill S.R., Dougherty B.A., Nelson K.E., Quackenbush J., Zhou L., Kirkness E.F., Peterson S.N., Loftus B.J., Richardson D.L., Dodson R.J. , Khalak H.G., Glodek A., McKenney K., FitzGerald L.M., Lee N., Adams M.D., Hickey E.K., Berg D.E., Gocayne J.D., Utterback T.R., Peterson J.D., Kelley J.M., Cotton M.D., Weidman J.F., Fujii C., Bowman C., Watthey L., Wallin E., Hayes W.S., Borodovsky M., Karp P.D., Smith H.O., Fraser C.M., Venter J.C. Nature 388:539-547(1997) [PubMed: 9252185] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 700392 / 26695.
[4]	"Insertion of mini-IS605 and deletion of adjacent sequences in the nitroreductase (rdxA) gene cause metronidazole resistance in Helicobacter pylori NCTC11637." Debets-Ossenkopp Y.J., Pot R.G.J., van Westerloo D.J., Goodwin A., Vandenbroucke-Grauls C.M.J.E., Berg D.E., Hoffman P.S., Kusters J.G. Antimicrob. Agents Chemother. 43:2657-2662(1999) [PubMed: 10543743] [Abstract] Cited for: INVOLVEMENT IN RESISTANCE TO METRONIDAZOLE. Strain: ATCC 43504 / NCTC 11637 / JCM 7653 / RPH 13487.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF012552 Genomic DNA. Translation: AAC46349.1. AF315501 Genomic DNA. Translation: AAK17124.1. AF315502 Genomic DNA. Translation: AAK17125.1. AF316109 Genomic DNA. Translation: AAK19260.1. AE000511 Genomic DNA. Translation: AAD07997.1.
PIR	B64639.
RefSeq	NP_207746.1. NC_000915.1.
3D structure databases
ProteinModelPortal	O25608.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-3602N.
MINT	MINT-179377.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	899487.
GenomeReviews	Gene locus HP_0954 in contig AE000511_GR.
KEGG	hpy:HP0954.
NMPDR	fig|85962.1.peg.943.
PATRIC	20593221. VBIHelPyl33062_0992.
TIGR	HP_0954.
Phylogenomic databases
HOGENOM	HBG501873.
OMA	ATAKGWA.
ProtClustDB	CLSK496297.
Family and domain databases
InterPro	IPR000415. Nitroreductase-like. [Graphical view]
Gene3D	G3DSA:3.40.109.10. G3DSA:3.40.109.10. 1 hit.
Pfam	PF00881. Nitroreductase. 1 hit. [Graphical view]
SUPFAM	SSF55469. Nitroreductase. 1 hit.
ProtoNet	Search...

Entry information

Entry name

RDXA_HELPY

Accession

Primary (citable) accession number: O25608
Secondary accession number(s): O30585 , Q9AHD6, Q9AHF7, Q9AHF8

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 26, 2008
Last sequence update:	January 1, 1998
Last modified:	January 25, 2012
This is version 55 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program