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Protein

Dihydropteroate synthase

Gene

folP1

Organism
Mycobacterium leprae (strain TN)
Status
Reviewed-Annotation score: -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)DescriptionActionsGraphical viewLength
    Metal bindingi13MagnesiumBy similarity1
    Binding sitei536-hydroxymethyl-7,8-dihydropterin diphosphateBy similarity1
    Binding sitei866-hydroxymethyl-7,8-dihydropterin diphosphateBy similarity1
    Binding sitei1056-hydroxymethyl-7,8-dihydropterin diphosphateBy similarity1
    Binding sitei1776-hydroxymethyl-7,8-dihydropterin diphosphateBy similarity1
    Binding sitei2136-hydroxymethyl-7,8-dihydropterin diphosphateBy similarity1

    GO - Molecular functioni

    GO - Biological processi

    Keywordsi

    Molecular functionTransferase
    Biological processFolate biosynthesis
    LigandMagnesium, Metal-binding

    Enzyme and pathway databases

    BioCyciMLEP272631:G1GT5-255-MONOMER
    BRENDAi2.5.1.15 3504
    SABIO-RKiP0C0X1
    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 databases

    ChEMBLiCHEMBL2362993
    DrugBankiDB00250 Dapsone

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001682131 – 284Dihydropteroate synthaseAdd BLAST284

    Interactioni

    Subunit structurei

    Homodimer.1 Publication

    Protein-protein interaction databases

    STRINGi272631.ML0224

    Structurei

    3D structure databases

    ProteinModelPortaliP0C0X1
    SMRiP0C0X1
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini6 – 265Pterin-bindingPROSITE-ProRule annotationAdd BLAST260

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni253 – 2556-hydroxymethyl-7,8-dihydropterin diphosphate bindingBy similarity3

    Sequence similaritiesi

    Belongs to the DHPS family.Curated

    Phylogenomic databases

    eggNOGiENOG4105EEI Bacteria
    COG0294 LUCA
    HOGENOMiHOG000217509
    KOiK00796
    OMAiWAVRVHD
    OrthoDBiPOG091H00BJ

    Family and domain databases

    CDDicd00739 DHPS, 1 hit
    Gene3Di3.20.20.20, 1 hit
    InterProiView protein in InterPro
    IPR006390 DHP_synth
    IPR011005 Dihydropteroate_synth-like
    IPR000489 Pterin-binding_dom
    PfamiView protein in Pfam
    PF00809 Pterin_bind, 1 hit
    SUPFAMiSSF51717 SSF51717, 1 hit
    TIGRFAMsiTIGR01496 DHPS, 1 hit
    PROSITEiView protein in PROSITE
    PS00792 DHPS_1, 1 hit
    PS00793 DHPS_2, 1 hit
    PS50972 PTERIN_BINDING, 1 hit

    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)DescriptionActionsGraphical viewLength
    Sequence conflicti53T → A in BAA84081 (PubMed:10474189).Curated1
    Sequence conflicti53T → I in BAA84080 (PubMed:10474189).Curated1
    Sequence conflicti53T → I in BAA84079 (PubMed:10474189).Curated1
    Sequence conflicti55P → L in BAA84078 (PubMed:10474189).Curated1
    Sequence conflicti55P → L in BAA84077 (PubMed:10474189).Curated1
    Sequence conflicti55P → L in BAA84076 (PubMed:10474189).Curated1

    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
    PATRICifig|272631.5.peg.356

    Similar proteinsi

    Entry informationi

    Entry nameiDHPS1_MYCLE
    AccessioniPrimary (citable) accession number: P0C0X1
    Secondary accession number(s): O69530
    , P46812, Q9R2Q6, Q9R2U9, Q9S0T0
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 10, 2006
    Last sequence update: January 10, 2006
    Last modified: March 28, 2018
    This is version 83 of the entry and version 1 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome
    UniProt is an ELIXIR core data resource
    Main funding by: National Institutes of Health