DHPS1_MYCTO
ID DHPS1_MYCTO Reviewed; 280 AA.
AC P9WND0; L0TG01; O06274; P0A578;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 41.
DE RecName: Full=Dihydropteroate synthase;
DE Short=DHPS;
DE EC=2.5.1.15;
DE AltName: Full=Dihydropteroate pyrophosphorylase;
GN Name=folP1; OrderedLocusNames=MT3712;
OS Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83331;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CDC 1551 / Oshkosh;
RX PubMed=12218036; DOI=10.1128/jb.184.19.5479-5490.2002;
RA Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O.,
RA Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K.,
RA Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L.,
RA Delcher A., Utterback T.R., Weidman J.F., Khouri H.M., Gill J., Mikula A.,
RA Bishai W., Jacobs W.R. Jr., Venter J.C., Fraser C.M.;
RT "Whole-genome comparison of Mycobacterium tuberculosis clinical and
RT laboratory strains.";
RL J. Bacteriol. 184:5479-5490(2002).
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 (H2Pte), the immediate precursor of folate derivatives.
CC {ECO:0000250|UniProtKB:P9WND1}.
CC -!- FUNCTION: Is involved in the bioactivation of the antituberculous drug
CC para-aminosalicylic acid (PAS). PAS is a close structural analog of
CC pABA and acts as an alternative substrate for DHPS, leading to hydroxy-
CC dihydropteroate (H2PtePAS). Metabolomic studies show that PAS, despite
CC its in vitro activity as a competitive inhibitor of DHPS, does not
CC inhibit growth of M.tuberculosis by inhibiting DHPS. PAS exerts its
CC antimycobacterial activity through its effects on M.tuberculosis folate
CC metabolism downstream of DHPS. PAS poisons folate-dependent pathways
CC not only by serving as a replacement substrate for DHPS but also by the
CC products of that reaction serving as replacement substrates and/or
CC inhibitors of subsequent enzymes. {ECO:0000250|UniProtKB:P9WND1}.
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:0000250|UniProtKB:P9WND1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(7,8-dihydropterin-6-yl)methyl diphosphate + 4-aminosalicylate
CC = 2-hydroxy-7,8-dihydropteroate + diphosphate; Xref=Rhea:RHEA:53732,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:72950, ChEBI:CHEBI:137598,
CC ChEBI:CHEBI:137600; Evidence={ECO:0000250|UniProtKB:P9WND1};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P9WND1};
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 -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P9WND1}.
CC -!- SIMILARITY: Belongs to the DHPS family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK48071.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AE000516; AAK48071.1; ALT_INIT; Genomic_DNA.
DR PIR; A70956; A70956.
DR RefSeq; WP_003899596.1; NZ_KK341227.1.
DR AlphaFoldDB; P9WND0; -.
DR SMR; P9WND0; -.
DR EnsemblBacteria; AAK48071; AAK48071; MT3712.
DR GeneID; 45427594; -.
DR KEGG; mtc:MT3712; -.
DR PATRIC; fig|83331.31.peg.3996; -.
DR HOGENOM; CLU_008023_0_1_11; -.
DR UniPathway; UPA00077; UER00156.
DR Proteomes; UP000001020; 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 3: Inferred from homology;
KW Folate biosynthesis; Magnesium; Metal-binding; Transferase.
FT CHAIN 1..280
FT /note="Dihydropteroate synthase"
FT /id="PRO_0000427148"
FT DOMAIN 1..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 86
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000250|UniProtKB:P9WND1"
FT BINDING 105
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000250|UniProtKB:P9WND1"
FT BINDING 177
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000250|UniProtKB:P9WND1"
FT BINDING 213
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000250|UniProtKB:P9WND1"
FT BINDING 253..255
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000250|UniProtKB:P9WND1"
SQ SEQUENCE 280 AA; 28843 MW; 737AB6DF12C51C8C CRC64;
MSPAPVQVMG VLNVTDDSFS DGGCYLDLDD AVKHGLAMAA AGAGIVDVGG ESSRPGATRV
DPAVETSRVI PVVKELAAQG ITVSIDTMRA DVARAALQNG AQMVNDVSGG RADPAMGPLL
AEADVPWVLM HWRAVSADTP HVPVRYGNVV AEVRADLLAS VADAVAAGVD PARLVLDPGL
GFAKTAQHNW AILHALPELV ATGIPVLVGA SRKRFLGALL AGPDGVMRPT DGRDTATAVI
SALAALHGAW GVRVHDVRAS VDAIKVVEAW MGAERIERDG
