DHPRS_HELPY
ID DHPRS_HELPY Reviewed; 380 AA.
AC O25830;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Bifunctional dihydropteroate synthase/dihydropteroate reductase;
DE Includes:
DE RecName: Full=Dihydropteroate reductase {ECO:0000303|PubMed:15554970};
DE Short=DHPR {ECO:0000303|PubMed:17416665};
DE EC=1.5.8.- {ECO:0000269|PubMed:17416665};
DE Includes:
DE RecName: Full=Dihydropteroate synthase {ECO:0000303|PubMed:15554970};
DE Short=DHPS {ECO:0000303|PubMed:15554970};
DE EC=2.5.1.15 {ECO:0000269|PubMed:17416665};
DE AltName: Full=Dihydropteroate pyrophosphorylase;
GN Name=folP {ECO:0000303|PubMed:17416665};
GN OrderedLocusNames=C694_06360, HP_1232;
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 [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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700392 / 26695;
RA Manolov A., Prihodko E., Larin A., Karpova I., Semashko T., Alexeev D.,
RA Kostrjukova E., Govorun V.;
RT "Draft genome of Helicobacter pylori.";
RL Submitted (OCT-2012) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION.
RX PubMed=15554970; DOI=10.1111/j.1365-2958.2004.04339.x;
RA Levin I., Giladi M., Altman-Price N., Ortenberg R., Mevarech M.;
RT "An alternative pathway for reduced folate biosynthesis in bacteria and
RT halophilic archaea.";
RL Mol. Microbiol. 54:1307-1318(2004).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND MUTAGENESIS OF MET-28; LYS-31;
RP LYS-51; GLY-58 AND LYS-92.
RX PubMed=17416665; DOI=10.1128/jb.01878-06;
RA Levin I., Mevarech M., Palfey B.A.;
RT "Characterization of a novel bifunctional dihydropteroate
RT synthase/dihydropteroate reductase enzyme from Helicobacter pylori.";
RL J. Bacteriol. 189:4062-4069(2007).
CC -!- FUNCTION: Bifunctional enzyme that catalyzes the formation of
CC dihydropteroate, the immediate precursor of folic acid and the
CC reduction of dihydropteroate to tetrahydropteroate.
CC {ECO:0000269|PubMed:15554970, ECO:0000269|PubMed:17416665}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(7,8-dihydropterin-6-yl)methyl diphosphate + 4-aminobenzoate =
CC 7,8-dihydropteroate + diphosphate; Xref=Rhea:RHEA:19949,
CC ChEBI:CHEBI:17836, ChEBI:CHEBI:17839, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:72950; EC=2.5.1.15;
CC Evidence={ECO:0000269|PubMed:17416665};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-5,6,7,8-tetrahydropteroate + NAD(+) = 7,8-dihydropteroate
CC + H(+) + NADH; Xref=Rhea:RHEA:45744, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17839, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:85414; Evidence={ECO:0000269|PubMed:17416665};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:17416665};
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000269|PubMed:17416665};
CC Note=Binds 1 FAD or 1 FMN per subunit. {ECO:0000269|PubMed:17416665};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P0AC13};
CC -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 7,8-
CC dihydrofolate from 2-amino-4-hydroxy-6-hydroxymethyl-7,8-
CC dihydropteridine diphosphate and 4-aminobenzoate: step 1/2.
CC -!- DOMAIN: The N-terminal extension of FolP is essential for the reducing
CC activity and binds FMN.
CC -!- MISCELLANEOUS: FolP can complement an E.coli strain in which the two
CC distinct genes encoding dihydrofolate reductases folA and folM are
CC deleted. {ECO:0000305|PubMed:17416665}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the DHPS family.
CC {ECO:0000305}.
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DR EMBL; AE000511; AAD08276.1; -; Genomic_DNA.
DR EMBL; CP003904; AFV42447.1; -; Genomic_DNA.
DR PIR; H64673; H64673.
DR RefSeq; NP_208024.1; NC_000915.1.
DR RefSeq; WP_000636048.1; NC_018939.1.
DR AlphaFoldDB; O25830; -.
DR SMR; O25830; -.
DR DIP; DIP-3693N; -.
DR IntAct; O25830; 1.
DR MINT; O25830; -.
DR STRING; 85962.C694_06360; -.
DR PaxDb; O25830; -.
DR EnsemblBacteria; AAD08276; AAD08276; HP_1232.
DR KEGG; heo:C694_06360; -.
DR KEGG; hpy:HP_1232; -.
DR PATRIC; fig|85962.47.peg.1320; -.
DR eggNOG; COG0294; Bacteria.
DR HOGENOM; CLU_008023_1_0_7; -.
DR OMA; FSIDTYH; -.
DR PhylomeDB; O25830; -.
DR BioCyc; MetaCyc:HP_RS06080-MON; -.
DR UniPathway; UPA00077; UER00156.
DR Proteomes; UP000000429; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0004156; F:dihydropteroate synthase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0046656; P:folic acid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IBA:GO_Central.
DR CDD; cd00739; DHPS; 1.
DR Gene3D; 3.20.20.20; -; 1.
DR InterPro; IPR045031; DHP_synth.
DR InterPro; IPR006390; DHP_synth_dom.
DR InterPro; IPR011005; Dihydropteroate_synth-like.
DR InterPro; IPR016227; Dihydropteroate_synthase_prd.
DR InterPro; IPR000489; Pterin-binding_dom.
DR PANTHER; PTHR20941; PTHR20941; 1.
DR Pfam; PF00809; Pterin_bind; 1.
DR PIRSF; PIRSF000501; DHPS_Campy_prd; 1.
DR SUPFAM; SSF51717; SSF51717; 1.
DR TIGRFAMs; TIGR01496; DHPS; 1.
DR PROSITE; PS50972; PTERIN_BINDING; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; FMN; Folate biosynthesis; Magnesium; Metal-binding;
KW Multifunctional enzyme; NAD; Oxidoreductase; Reference proteome;
KW Transferase.
FT CHAIN 1..380
FT /note="Bifunctional dihydropteroate
FT synthase/dihydropteroate reductase"
FT /id="PRO_0000428675"
FT DOMAIN 119..371
FT /note="Pterin-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00334"
FT REGION 1..104
FT /note="Dihydropteroate reductase"
FT REGION 105..380
FT /note="Dihydropteroate synthase"
FT BINDING 126
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P9WND1"
FT BINDING 202
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000250|UniProtKB:P0AC13"
FT BINDING 221
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000250|UniProtKB:P0AC13"
FT BINDING 289
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000250|UniProtKB:P0AC13"
FT BINDING 325
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000250|UniProtKB:P0AC13"
FT BINDING 359..361
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000250|UniProtKB:P0AC13"
FT MUTAGEN 28
FT /note="M->A: Unable to bind FMN."
FT /evidence="ECO:0000269|PubMed:17416665"
FT MUTAGEN 31
FT /note="K->A: Unable to bind FMN."
FT /evidence="ECO:0000269|PubMed:17416665"
FT MUTAGEN 51
FT /note="K->A: Unstable protein."
FT /evidence="ECO:0000269|PubMed:17416665"
FT MUTAGEN 58
FT /note="G->A: No effect."
FT /evidence="ECO:0000269|PubMed:17416665"
FT MUTAGEN 92
FT /note="K->E: Unable to bind FMN."
FT /evidence="ECO:0000269|PubMed:17416665"
SQ SEQUENCE 380 AA; 43275 MW; 618C39DFDA39B174 CRC64;
MIVKRLNPDA LKNALQKIGP EKIAQDRMHQ KGVSFVFEIQ HLPLSATLIL KQEAISVGGD
FATPRDCILA KEPFYDGVLI ASAKQLERLI VKCHSQPFGL KHLAQELKSH LKAPKPNTPQ
IMAVLNLTPD SFYEKSRFDS KKALEEIYQW LEKGITLIDI GAASSRPESE IIDPKIEQDR
LKEILLEIKS QKLYQCAKFS IDTYHATTAQ MALEHYFSIL NDVSGFNSAE MLEVAKDYKP
TCILMHTQKT PKDMQENVFY HNLFDEMDRF FKEKLEVLEK YVLQDIILDI GFGFAKLKEH
NLALIKHLSH FLKFKKPLLV GASRKNTIGL ITGREVQDRL AGTLSLHLMA LQNGASVLRV
HDIDEHIDLI KVFKSLEETD
