Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Dihydropteroate synthase

Gene

folP

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the condensation of para-aminobenzoate (pABA) with 6-hydroxymethyl-7,8-dihydropterin diphosphate (DHPt-PP) to form 7,8-dihydropteroate (H2Pte), the immediate precursor of folate derivatives.1 Publication

Catalytic activityi

6-hydroxymethyl-7,8-dihydropterin diphosphate + 4-aminobenzoate = diphosphate + dihydropteroate.2 Publications

Cofactori

Mg2+1 PublicationNote: Magnesium is required for activity, even if it seems to interact primarily with the substrate.Curated1 Publication

Kineticsi

  1. KM=2.5 µM for 4-aminobenzoate1 Publication

    pH dependencei

    Optimum pH is 8.5.1 Publication

    Pathwayi: tetrahydrofolate biosynthesis

    This protein is involved in step 1 of the subpathway that synthesizes 7,8-dihydrofolate from 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine diphosphate and 4-aminobenzoate.
    Proteins known to be involved in the 2 steps of the subpathway in this organism are:
    1. Dihydropteroate synthase (folP)
    2. Bifunctional protein FolC (folC)
    This subpathway is part of the pathway tetrahydrofolate biosynthesis, which is itself part of Cofactor biosynthesis.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes 7,8-dihydrofolate from 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine diphosphate and 4-aminobenzoate, the pathway tetrahydrofolate biosynthesis and in Cofactor biosynthesis.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi22 – 221MagnesiumBy similarity
    Binding sitei62 – 6216-hydroxymethyl-7,8-dihydropterin diphosphateCombined sources1 Publication
    Binding sitei96 – 9616-hydroxymethyl-7,8-dihydropterin diphosphateCombined sources1 Publication
    Binding sitei115 – 11516-hydroxymethyl-7,8-dihydropterin diphosphateCombined sources1 Publication
    Binding sitei185 – 18516-hydroxymethyl-7,8-dihydropterin diphosphateCombined sources1 Publication
    Binding sitei221 – 22116-hydroxymethyl-7,8-dihydropterin diphosphateCombined sources1 Publication

    GO - Molecular functioni

    • dihydropteroate synthase activity Source: EcoliWiki
    • metal ion binding Source: UniProtKB-KW

    GO - Biological processi

    • folic acid biosynthetic process Source: EcoCyc
    • response to drug Source: EcoliWiki
    • tetrahydrofolate biosynthetic process Source: UniProtKB-UniPathway
    Complete GO annotation...

    Keywords - Molecular functioni

    Transferase

    Keywords - Biological processi

    Folate biosynthesis

    Keywords - Ligandi

    Magnesium, Metal-binding

    Enzyme and pathway databases

    BioCyciEcoCyc:H2PTEROATESYNTH-MONOMER.
    ECOL316407:JW3144-MONOMER.
    MetaCyc:H2PTEROATESYNTH-MONOMER.
    BRENDAi2.5.1.15. 2167.
    SABIO-RKP0AC13.
    UniPathwayiUPA00077; UER00156.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Dihydropteroate synthase1 Publication (EC:2.5.1.151 Publication)
    Short name:
    DHPS1 Publication
    Alternative name(s):
    Dihydropteroate pyrophosphorylase
    Gene namesi
    Name:folP
    Synonyms:dhpS
    Ordered Locus Names:b3177, JW3144
    OrganismiEscherichia coli (strain K12)
    Taxonomic identifieri83333 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia
    Proteomesi
    • UP000000318 Componenti: Chromosome
    • UP000000625 Componenti: Chromosome

    Organism-specific databases

    EcoGeneiEG50011. folP.

    Subcellular locationi

    GO - Cellular componenti

    • cytoplasm Source: EcoliWiki
    • cytosol Source: EcoCyc
    Complete GO annotation...

    Pathology & Biotechi

    Chemistry

    ChEMBLiCHEMBL2364668.
    DrugBankiDB00634. Sulfacetamide.
    DB01298. Sulfacytine.
    DB01581. Sulfamerazine.
    DB01582. Sulfamethazine.
    DB00576. Sulfamethizole.
    DB01015. Sulfamethoxazole.
    DB00259. Sulfanilamide.
    DB06729. Sulfaphenazole.
    DB00263. Sulfisoxazole.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 282282Dihydropteroate synthasePRO_0000168207Add
    BLAST

    Proteomic databases

    EPDiP0AC13.
    PaxDbiP0AC13.
    PRIDEiP0AC13.

    Interactioni

    Subunit structurei

    Homodimer.2 Publications

    Protein-protein interaction databases

    DIPiDIP-47922N.
    IntActiP0AC13. 1 interaction.
    MINTiMINT-1268009.
    STRINGi511145.b3177.

    Chemistry

    BindingDBiP0AC13.

    Structurei

    Secondary structure

    1
    282
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi2 – 54Combined sources
    Beta strandi8 – 114Combined sources
    Beta strandi16 – 227Combined sources
    Turni25 – 273Combined sources
    Helixi29 – 335Combined sources
    Helixi36 – 5015Combined sources
    Beta strandi53 – 608Combined sources
    Helixi71 – 8818Combined sources
    Beta strandi92 – 965Combined sources
    Helixi100 – 1089Combined sources
    Beta strandi113 – 1164Combined sources
    Turni117 – 1204Combined sources
    Helixi125 – 1328Combined sources
    Beta strandi136 – 1394Combined sources
    Helixi157 – 17418Combined sources
    Helixi179 – 1813Combined sources
    Beta strandi182 – 1854Combined sources
    Helixi194 – 2029Combined sources
    Helixi204 – 2107Combined sources
    Beta strandi214 – 2163Combined sources
    Helixi222 – 2287Combined sources
    Helixi232 – 2343Combined sources
    Helixi236 – 24813Combined sources
    Beta strandi252 – 2576Combined sources
    Helixi259 – 27517Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1AJ0X-ray2.00A1-282[»]
    1AJ2X-ray2.00A1-282[»]
    1AJZX-ray2.00A1-282[»]
    ProteinModelPortaliP0AC13.
    SMRiP0AC13. Positions 1-282.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP0AC13.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini15 – 267253Pterin-bindingPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni255 – 25736-hydroxymethyl-7,8-dihydropterin diphosphate bindingCombined sources1 Publication

    Sequence similaritiesi

    Belongs to the DHPS family.Curated
    Contains 1 pterin-binding domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiENOG4105EEI. Bacteria.
    COG0294. LUCA.
    HOGENOMiHOG000217510.
    InParanoidiP0AC13.
    KOiK00796.
    OMAiSIDTYHA.
    OrthoDBiEOG67T5P5.
    PhylomeDBiP0AC13.

    Family and domain databases

    Gene3Di3.20.20.20. 1 hit.
    InterProiIPR006390. DHP_synth.
    IPR011005. Dihydropteroate_synth-like.
    IPR000489. Pterin-binding_dom.
    [Graphical view]
    PfamiPF00809. Pterin_bind. 1 hit.
    [Graphical view]
    SUPFAMiSSF51717. SSF51717. 1 hit.
    TIGRFAMsiTIGR01496. DHPS. 1 hit.
    PROSITEiPS00792. DHPS_1. 1 hit.
    PS00793. DHPS_2. 1 hit.
    PS50972. PTERIN_BINDING. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P0AC13-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MKLFAQGTSL DLSHPHVMGI LNVTPDSFSD GGTHNSLIDA VKHANLMINA
    60 70 80 90 100
    GATIIDVGGE STRPGAAEVS VEEELQRVIP VVEAIAQRFE VWISVDTSKP
    110 120 130 140 150
    EVIRESAKVG AHIINDIRSL SEPGALEAAA ETGLPVCLMH MQGNPKTMQE
    160 170 180 190 200
    APKYDDVFAE VNRYFIEQIA RCEQAGIAKE KLLLDPGFGF GKNLSHNYSL
    210 220 230 240 250
    LARLAEFHHF NLPLLVGMSR KSMIGQLLNV GPSERLSGSL ACAVIAAMQG
    260 270 280
    AHIIRVHDVK ETVEAMRVVE ATLSAKENKR YE
    Length:282
    Mass (Da):30,615
    Last modified:November 8, 2005 - v1
    Checksum:i6230C8883796F59E
    GO

    Sequence cautioni

    The sequence AAA57978.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti6 – 61Q → E AA sequence (PubMed:1657875).Curated
    Sequence conflicti77 – 771R → A in AAA97509 (Ref. 3) Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti28 – 281F → I in TS20; resistant to sulfonamide and temperature-sensitive.

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X68776 Genomic DNA. Translation: CAA48676.1.
    X68777 Genomic DNA. Translation: CAA48677.1.
    L06494 Genomic DNA. Translation: AAA23804.1.
    L12968 Unassigned DNA. Translation: AAA16123.1.
    U01376 Genomic DNA. Translation: AAA97509.1.
    U18997 Genomic DNA. Translation: AAA57978.1. Different initiation.
    U00096 Genomic DNA. Translation: AAC76209.2.
    AP009048 Genomic DNA. Translation: BAE77221.1.
    PIRiA43326.
    RefSeqiNP_417644.4. NC_000913.3.
    WP_000764731.1. NZ_LN832404.1.

    Genome annotation databases

    EnsemblBacteriaiAAC76209; AAC76209; b3177.
    BAE77221; BAE77221; BAE77221.
    GeneIDi947691.
    KEGGiecj:JW3144.
    eco:b3177.
    PATRICi32121772. VBIEscCol129921_3270.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X68776 Genomic DNA. Translation: CAA48676.1.
    X68777 Genomic DNA. Translation: CAA48677.1.
    L06494 Genomic DNA. Translation: AAA23804.1.
    L12968 Unassigned DNA. Translation: AAA16123.1.
    U01376 Genomic DNA. Translation: AAA97509.1.
    U18997 Genomic DNA. Translation: AAA57978.1. Different initiation.
    U00096 Genomic DNA. Translation: AAC76209.2.
    AP009048 Genomic DNA. Translation: BAE77221.1.
    PIRiA43326.
    RefSeqiNP_417644.4. NC_000913.3.
    WP_000764731.1. NZ_LN832404.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1AJ0X-ray2.00A1-282[»]
    1AJ2X-ray2.00A1-282[»]
    1AJZX-ray2.00A1-282[»]
    ProteinModelPortaliP0AC13.
    SMRiP0AC13. Positions 1-282.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    DIPiDIP-47922N.
    IntActiP0AC13. 1 interaction.
    MINTiMINT-1268009.
    STRINGi511145.b3177.

    Chemistry

    BindingDBiP0AC13.
    ChEMBLiCHEMBL2364668.
    DrugBankiDB00634. Sulfacetamide.
    DB01298. Sulfacytine.
    DB01581. Sulfamerazine.
    DB01582. Sulfamethazine.
    DB00576. Sulfamethizole.
    DB01015. Sulfamethoxazole.
    DB00259. Sulfanilamide.
    DB06729. Sulfaphenazole.
    DB00263. Sulfisoxazole.

    Proteomic databases

    EPDiP0AC13.
    PaxDbiP0AC13.
    PRIDEiP0AC13.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiAAC76209; AAC76209; b3177.
    BAE77221; BAE77221; BAE77221.
    GeneIDi947691.
    KEGGiecj:JW3144.
    eco:b3177.
    PATRICi32121772. VBIEscCol129921_3270.

    Organism-specific databases

    EchoBASEiEB4304.
    EcoGeneiEG50011. folP.

    Phylogenomic databases

    eggNOGiENOG4105EEI. Bacteria.
    COG0294. LUCA.
    HOGENOMiHOG000217510.
    InParanoidiP0AC13.
    KOiK00796.
    OMAiSIDTYHA.
    OrthoDBiEOG67T5P5.
    PhylomeDBiP0AC13.

    Enzyme and pathway databases

    UniPathwayiUPA00077; UER00156.
    BioCyciEcoCyc:H2PTEROATESYNTH-MONOMER.
    ECOL316407:JW3144-MONOMER.
    MetaCyc:H2PTEROATESYNTH-MONOMER.
    BRENDAi2.5.1.15. 2167.
    SABIO-RKP0AC13.

    Miscellaneous databases

    EvolutionaryTraceiP0AC13.
    PROiP0AC13.

    Family and domain databases

    Gene3Di3.20.20.20. 1 hit.
    InterProiIPR006390. DHP_synth.
    IPR011005. Dihydropteroate_synth-like.
    IPR000489. Pterin-binding_dom.
    [Graphical view]
    PfamiPF00809. Pterin_bind. 1 hit.
    [Graphical view]
    SUPFAMiSSF51717. SSF51717. 1 hit.
    TIGRFAMsiTIGR01496. DHPS. 1 hit.
    PROSITEiPS00792. DHPS_1. 1 hit.
    PS00793. DHPS_2. 1 hit.
    PS50972. PTERIN_BINDING. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Point mutations in the dihydropteroate synthase gene causing sulfonamide resistance."
      Swedberg G., Fermer C., Skoeld O.
      Adv. Exp. Med. Biol. 338:555-558(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: C-167.
    2. "Cloning, sequencing, and enhanced expression of the dihydropteroate synthase gene of Escherichia coli MC4100."
      Dallas W.S., Gowen J.E., Ray P.H., Cox M.J., Dev I.K.
      J. Bacteriol. 174:5961-5970(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
    3. Wang R., Kushner S.R.
      Submitted (SEP-1993) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: K12.
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / MG1655 / ATCC 47076.
    5. "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110."
      Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.
      Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
    6. "Purification and partial characterization of 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase and 7,8-dihydropteroate synthase from Escherichia coli MC4100."
      Talarico T.L., Dev I.K., Dallas W.S., Ferone R., Ray P.H.
      J. Bacteriol. 173:7029-7032(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 1-28.
      Strain: K12 / MC4100 / ATCC 35695 / DSM 6574.
    7. "The biosynthesis of folic acid. IX. Purification and properties of the enzymes required for the formation of dihydropteroic acid."
      Richey D.P., Brown G.M.
      J. Biol. Chem. 244:1582-1592(1969) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT.
    8. "Characterization of mutationally altered dihydropteroate synthase and its ability to form a sulfonamide-containing dihydrofolate analog."
      Swedberg G., Castensson S., Skold O.
      J. Bacteriol. 137:129-136(1979) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY, FUNCTION.
      Strain: C-167.
    9. "Crystal structure of the anti-bacterial sulfonamide drug target dihydropteroate synthase."
      Achari A., Somers D.O., Champness J.N., Bryant P.K., Rosemond J., Stammers D.K.
      Nat. Struct. Biol. 4:490-497(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEXES WITH SUBSTRATE; SULFANILAMIDE AND SUBSTRATE ANALOG, SUBUNIT.

    Entry informationi

    Entry nameiDHPS_ECOLI
    AccessioniPrimary (citable) accession number: P0AC13
    Secondary accession number(s): P26282, P78110, Q2M935
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 8, 2005
    Last sequence update: November 8, 2005
    Last modified: May 11, 2016
    This is version 94 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Escherichia coli
      Escherichia coli (strain K12): entries and cross-references to EcoGene
    2. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.