DHPS1_MYCLE
ID DHPS1_MYCLE Reviewed; 284 AA.
AC P0C0X1; O69530; P46812; Q9R2Q6; Q9R2U9; Q9S0T0;
DT 10-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 10-JAN-2006, sequence version 1.
DT 03-AUG-2022, entry version 97.
DE RecName: Full=Dihydropteroate synthase {ECO:0000303|PubMed:10542185};
DE Short=DHPS {ECO:0000303|PubMed:10542185};
DE EC=2.5.1.15 {ECO:0000269|PubMed:10542185};
DE AltName: Full=Dihydropteroate pyrophosphorylase;
GN Name=folP1; Synonyms=folP; OrderedLocusNames=ML0224; ORFNames=MLCB2548.07c;
OS Mycobacterium leprae (strain TN).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium.
OX NCBI_TaxID=272631;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10474189; DOI=10.1111/j.1574-6968.1999.tb13737.x;
RA Kai M., Matsuoka M., Nakata N., Maeda S., Gidoh M., Maeda Y., Hashimoto K.,
RA Kobayashi K., Kashiwabara Y.;
RT "Diaminodiphenylsulfone resistance of Mycobacterium leprae due to mutations
RT in the dihydropteroate synthase gene.";
RL FEMS Microbiol. Lett. 177:231-235(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, AND SUBUNIT.
RX PubMed=10542185; DOI=10.1128/jb.181.21.6814-6821.1999;
RA Nopponpunth V., Sirawaraporn W., Greene P.J., Santi D.V.;
RT "Cloning and expression of Mycobacterium tuberculosis and Mycobacterium
RT leprae dihydropteroate synthase in Escherichia coli.";
RL J. Bacteriol. 181:6814-6821(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=TN;
RX PubMed=11234002; DOI=10.1038/35059006;
RA Cole S.T., Eiglmeier K., Parkhill J., James K.D., Thomson N.R.,
RA Wheeler P.R., Honore N., Garnier T., Churcher C.M., Harris D.E.,
RA Mungall K.L., Basham D., Brown D., Chillingworth T., Connor R.,
RA Davies R.M., Devlin K., Duthoy S., Feltwell T., Fraser A., Hamlin N.,
RA Holroyd S., Hornsby T., Jagels K., Lacroix C., Maclean J., Moule S.,
RA Murphy L.D., Oliver K., Quail M.A., Rajandream M.A., Rutherford K.M.,
RA Rutter S., Seeger K., Simon S., Simmonds M., Skelton J., Squares R.,
RA Squares S., Stevens K., Taylor K., Whitehead S., Woodward J.R.,
RA Barrell B.G.;
RT "Massive gene decay in the leprosy bacillus.";
RL Nature 409:1007-1011(2001).
CC -!- FUNCTION: Catalyzes the condensation of para-aminobenzoate (pABA) with
CC 6-hydroxymethyl-7,8-dihydropterin diphosphate (DHPt-PP) to form 7,8-
CC dihydropteroate, the immediate precursor of folate derivatives.
CC {ECO:0000269|PubMed:10542185}.
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:10542185};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P0AC13};
CC -!- ACTIVITY REGULATION: Is potently inhibited by the sulfone dapsone and
CC the two sulfonamides sulfamethoxazole and sulfamethoxypyridazine, with
CC Kis in the range of 12 to 32 nM. To a lesser extent, is also inhibited
CC by p-aminosalicylate (PAS). {ECO:0000269|PubMed:10542185}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.6 uM for 4-aminobenzoate {ECO:0000269|PubMed:10542185};
CC KM=1.2 uM for 6-hydroxymethyl-7,8-dihydropterin diphosphate
CC {ECO:0000269|PubMed:10542185};
CC Note=kcat is 10.6 min(-1). {ECO:0000269|PubMed:10542185};
CC pH dependence:
CC Optimum pH is 9. {ECO:0000269|PubMed:10542185};
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 {ECO:0000305|PubMed:10542185}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:10542185}.
CC -!- SIMILARITY: Belongs to the DHPS family. {ECO:0000305}.
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DR EMBL; AB028658; BAA84076.1; -; Genomic_DNA.
DR EMBL; AB028659; BAA84077.1; -; Genomic_DNA.
DR EMBL; AB028660; BAA84078.1; -; Genomic_DNA.
DR EMBL; AB028661; BAA84079.1; -; Genomic_DNA.
DR EMBL; AB028662; BAA84080.1; -; Genomic_DNA.
DR EMBL; AB028663; BAA84081.1; -; Genomic_DNA.
DR EMBL; AB028656; BAA84074.1; -; Genomic_DNA.
DR EMBL; AB028657; BAA84075.1; -; Genomic_DNA.
DR EMBL; AF117618; AAF06725.1; -; Genomic_DNA.
DR EMBL; AL023093; CAA18794.1; -; Genomic_DNA.
DR EMBL; AL583917; CAC29732.1; -; Genomic_DNA.
DR PIR; H86936; H86936.
DR RefSeq; NP_301284.1; NC_002677.1.
DR RefSeq; WP_010907608.1; NC_002677.1.
DR AlphaFoldDB; P0C0X1; -.
DR SMR; P0C0X1; -.
DR STRING; 272631.ML0224; -.
DR ChEMBL; CHEMBL2362993; -.
DR DrugBank; DB00250; Dapsone.
DR DrugCentral; P0C0X1; -.
DR EnsemblBacteria; CAC29732; CAC29732; CAC29732.
DR KEGG; mle:ML0224; -.
DR PATRIC; fig|272631.5.peg.356; -.
DR Leproma; ML0224; -.
DR eggNOG; COG0294; Bacteria.
DR HOGENOM; CLU_008023_0_1_11; -.
DR OMA; FSIDTYH; -.
DR BRENDA; 2.5.1.15; 3504.
DR SABIO-RK; P0C0X1; -.
DR UniPathway; UPA00077; UER00156.
DR PRO; PR:P0C0X1; -.
DR Proteomes; UP000000806; Chromosome.
DR GO; GO:0004156; F:dihydropteroate synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0046656; P:folic acid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IEA:UniProtKB-UniPathway.
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; IPR000489; Pterin-binding_dom.
DR PANTHER; PTHR20941; PTHR20941; 1.
DR Pfam; PF00809; Pterin_bind; 1.
DR SUPFAM; SSF51717; SSF51717; 1.
DR TIGRFAMs; TIGR01496; DHPS; 1.
DR PROSITE; PS00792; DHPS_1; 1.
DR PROSITE; PS00793; DHPS_2; 1.
DR PROSITE; PS50972; PTERIN_BINDING; 1.
PE 1: Evidence at protein level;
KW Folate biosynthesis; Magnesium; Metal-binding; Reference proteome;
KW Transferase.
FT CHAIN 1..284
FT /note="Dihydropteroate synthase"
FT /id="PRO_0000168213"
FT DOMAIN 6..265
FT /note="Pterin-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00334"
FT BINDING 13
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P9WND1"
FT BINDING 53
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000250|UniProtKB:P0AC13"
FT BINDING 86
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000250|UniProtKB:P0AC13"
FT BINDING 105
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000250|UniProtKB:P0AC13"
FT BINDING 177
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000250|UniProtKB:P0AC13"
FT BINDING 213
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000250|UniProtKB:P0AC13"
FT BINDING 253..255
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000250|UniProtKB:P0AC13"
FT CONFLICT 53
FT /note="T -> A (in Ref. 1; BAA84081)"
FT /evidence="ECO:0000305"
FT CONFLICT 53
FT /note="T -> I (in Ref. 1; BAA84080/BAA84079)"
FT /evidence="ECO:0000305"
FT CONFLICT 55
FT /note="P -> L (in Ref. 1; BAA84078/BAA84077/BAA84076)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 284 AA; 29448 MW; A576FF46C16AC826 CRC64;
MSLAPVQVIG VLNVTDNSFS DGGRYLDPDD AVQHGLAMVA EGAAIVDVGG ESTRPGAIRT
DPRVELSRIV PVVKELAAQG ITVSIDTTRA DVARAALQSG ARIVNDVSGG RADPAMAPLV
AEAGVAWVLM HWRLMSAERP YEAPNYRDVV AEVRADLLAG VDQAVAAGVD PGSLVIDPGL
GFAKTGQHNW ALLNALPELV ATGVPILLGA SRKRFLGRLL AGADGAVRPP DGRETATAVI
SALAALHGAW GVRVHDVRAS VDALKVVGAW LHAGPQIEKV RCDG
