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 27-MAR-2024, entry version 104. 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; GN ORFNames=MLCB2548.07c; OS Mycobacterium leprae (strain TN). OC Bacteria; Actinomycetota; Actinomycetes; Mycobacteriales; 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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.gene:17574041; -. DR ChEMBL; CHEMBL2362993; -. DR DrugBank; DB00250; Dapsone. DR DrugCentral; P0C0X1; -. 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 OrthoDB; 9811744at2; -. 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; Dihydropteroate synthase-like; 1. DR InterPro; IPR045031; DHP_synth-like. DR InterPro; IPR006390; DHP_synth_dom. DR InterPro; IPR011005; Dihydropteroate_synth-like_sf. DR InterPro; IPR000489; Pterin-binding_dom. DR NCBIfam; TIGR01496; DHPS; 1. DR PANTHER; PTHR20941; FOLATE SYNTHESIS PROTEINS; 1. DR PANTHER; PTHR20941:SF1; FOLIC ACID SYNTHESIS PROTEIN FOL1; 1. DR Pfam; PF00809; Pterin_bind; 1. DR SUPFAM; SSF51717; Dihydropteroate synthetase-like; 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 //