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Protein

Dihydropteroate synthase

Gene

folP1

Organism
Mycobacterium leprae (strain TN)
Status
Reviewed-Annotation score: Annotation score: 4 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, the immediate precursor of folate derivatives.1 Publication

Catalytic activityi

6-hydroxymethyl-7,8-dihydropterin diphosphate + 4-aminobenzoate = diphosphate + dihydropteroate.1 Publication

Cofactori

Mg2+By similarity

Enzyme regulationi

Is potently inhibited by the sulfone dapsone and the two sulfonamides sulfamethoxazole and sulfamethoxypyridazine, with Kis in the range of 12 to 32 nM. To a lesser extent, is also inhibited by p-aminosalicylate (PAS).1 Publication

Kineticsi

kcat is 10.6 min(-1).1 Publication

  1. KM=0.6 µM for 4-aminobenzoate1 Publication
  2. KM=1.2 µM for 6-hydroxymethyl-7,8-dihydropterin diphosphate1 Publication

    pH dependencei

    Optimum pH is 9.1 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.1 Publication
    Proteins known to be involved in the 2 steps of the subpathway in this organism are:
    1. Dihydropteroate synthase (folP1)
    2. no protein annotated in this organism
    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 bindingi13 – 131MagnesiumBy similarity
    Binding sitei53 – 5316-hydroxymethyl-7,8-dihydropterin diphosphateBy similarity
    Binding sitei86 – 8616-hydroxymethyl-7,8-dihydropterin diphosphateBy similarity
    Binding sitei105 – 10516-hydroxymethyl-7,8-dihydropterin diphosphateBy similarity
    Binding sitei177 – 17716-hydroxymethyl-7,8-dihydropterin diphosphateBy similarity
    Binding sitei213 – 21316-hydroxymethyl-7,8-dihydropterin diphosphateBy similarity

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Transferase

    Keywords - Biological processi

    Folate biosynthesis

    Keywords - Ligandi

    Magnesium, Metal-binding

    Enzyme and pathway databases

    BRENDAi2.5.1.15. 3504.
    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:folP1
    Synonyms:folP
    Ordered Locus Names:ML0224
    ORF Names:MLCB2548.07c
    OrganismiMycobacterium leprae (strain TN)
    Taxonomic identifieri272631 [NCBI]
    Taxonomic lineageiBacteriaActinobacteriaCorynebacterialesMycobacteriaceaeMycobacterium
    Proteomesi
    • UP000000806 Componenti: Chromosome

    Organism-specific databases

    LepromaiML0224.

    Pathology & Biotechi

    Chemistry

    ChEMBLiCHEMBL2362993.
    DrugBankiDB00250. Dapsone.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 284284Dihydropteroate synthasePRO_0000168213Add
    BLAST

    Interactioni

    Subunit structurei

    Homodimer.1 Publication

    Protein-protein interaction databases

    STRINGi272631.ML0224.

    Structurei

    3D structure databases

    ProteinModelPortaliP0C0X1.
    SMRiP0C0X1. Positions 5-273.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini6 – 265260Pterin-bindingPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni253 – 25536-hydroxymethyl-7,8-dihydropterin diphosphate bindingBy similarity

    Sequence similaritiesi

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

    Phylogenomic databases

    eggNOGiENOG4105EEI. Bacteria.
    COG0294. LUCA.
    HOGENOMiHOG000217509.
    KOiK00796.
    OMAiSIDTYHA.
    OrthoDBiEOG67T5P5.

    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.

    P0C0X1-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MSLAPVQVIG VLNVTDNSFS DGGRYLDPDD AVQHGLAMVA EGAAIVDVGG
    60 70 80 90 100
    ESTRPGAIRT DPRVELSRIV PVVKELAAQG ITVSIDTTRA DVARAALQSG
    110 120 130 140 150
    ARIVNDVSGG RADPAMAPLV AEAGVAWVLM HWRLMSAERP YEAPNYRDVV
    160 170 180 190 200
    AEVRADLLAG VDQAVAAGVD PGSLVIDPGL GFAKTGQHNW ALLNALPELV
    210 220 230 240 250
    ATGVPILLGA SRKRFLGRLL AGADGAVRPP DGRETATAVI SALAALHGAW
    260 270 280
    GVRVHDVRAS VDALKVVGAW LHAGPQIEKV RCDG
    Length:284
    Mass (Da):29,448
    Last modified:January 10, 2006 - v1
    Checksum:iA576FF46C16AC826
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti53 – 531T → A in BAA84081 (PubMed:10474189).Curated
    Sequence conflicti53 – 531T → I in BAA84080 (PubMed:10474189).Curated
    Sequence conflicti53 – 531T → I in BAA84079 (PubMed:10474189).Curated
    Sequence conflicti55 – 551P → L in BAA84078 (PubMed:10474189).Curated
    Sequence conflicti55 – 551P → L in BAA84077 (PubMed:10474189).Curated
    Sequence conflicti55 – 551P → L in BAA84076 (PubMed:10474189).Curated

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB028658 Genomic DNA. Translation: BAA84076.1.
    AB028659 Genomic DNA. Translation: BAA84077.1.
    AB028660 Genomic DNA. Translation: BAA84078.1.
    AB028661 Genomic DNA. Translation: BAA84079.1.
    AB028662 Genomic DNA. Translation: BAA84080.1.
    AB028663 Genomic DNA. Translation: BAA84081.1.
    AB028656 Genomic DNA. Translation: BAA84074.1.
    AB028657 Genomic DNA. Translation: BAA84075.1.
    AF117618 Genomic DNA. Translation: AAF06725.1.
    AL023093 Genomic DNA. Translation: CAA18794.1.
    AL583917 Genomic DNA. Translation: CAC29732.1.
    PIRiH86936.
    RefSeqiNP_301284.1. NC_002677.1.
    WP_010907608.1. NC_002677.1.

    Genome annotation databases

    EnsemblBacteriaiCAC29732; CAC29732; CAC29732.
    GeneIDi908646.
    KEGGimle:ML0224.
    PATRICi18050810. VBIMycLep78757_0356.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB028658 Genomic DNA. Translation: BAA84076.1.
    AB028659 Genomic DNA. Translation: BAA84077.1.
    AB028660 Genomic DNA. Translation: BAA84078.1.
    AB028661 Genomic DNA. Translation: BAA84079.1.
    AB028662 Genomic DNA. Translation: BAA84080.1.
    AB028663 Genomic DNA. Translation: BAA84081.1.
    AB028656 Genomic DNA. Translation: BAA84074.1.
    AB028657 Genomic DNA. Translation: BAA84075.1.
    AF117618 Genomic DNA. Translation: AAF06725.1.
    AL023093 Genomic DNA. Translation: CAA18794.1.
    AL583917 Genomic DNA. Translation: CAC29732.1.
    PIRiH86936.
    RefSeqiNP_301284.1. NC_002677.1.
    WP_010907608.1. NC_002677.1.

    3D structure databases

    ProteinModelPortaliP0C0X1.
    SMRiP0C0X1. Positions 5-273.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi272631.ML0224.

    Chemistry

    ChEMBLiCHEMBL2362993.
    DrugBankiDB00250. Dapsone.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiCAC29732; CAC29732; CAC29732.
    GeneIDi908646.
    KEGGimle:ML0224.
    PATRICi18050810. VBIMycLep78757_0356.

    Organism-specific databases

    LepromaiML0224.

    Phylogenomic databases

    eggNOGiENOG4105EEI. Bacteria.
    COG0294. LUCA.
    HOGENOMiHOG000217509.
    KOiK00796.
    OMAiSIDTYHA.
    OrthoDBiEOG67T5P5.

    Enzyme and pathway databases

    UniPathwayiUPA00077; UER00156.
    BRENDAi2.5.1.15. 3504.

    Miscellaneous databases

    PROiP0C0X1.

    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. "Diaminodiphenylsulfone resistance of Mycobacterium leprae due to mutations in the dihydropteroate synthase gene."
      Kai M., Matsuoka M., Nakata N., Maeda S., Gidoh M., Maeda Y., Hashimoto K., Kobayashi K., Kashiwabara Y.
      FEMS Microbiol. Lett. 177:231-235(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "Cloning and expression of Mycobacterium tuberculosis and Mycobacterium leprae dihydropteroate synthase in Escherichia coli."
      Nopponpunth V., Sirawaraporn W., Greene P.J., Santi D.V.
      J. Bacteriol. 181:6814-6821(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, SUBUNIT.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: TN.

    Entry informationi

    Entry nameiDHPS1_MYCLE
    AccessioniPrimary (citable) accession number: P0C0X1
    Secondary accession number(s): O69530
    , P46812, Q9R2Q6, Q9R2U9, Q9S0T0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 10, 2006
    Last sequence update: January 10, 2006
    Last modified: June 8, 2016
    This is version 72 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

    Complete proteome, Reference proteome

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. 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.