DHPS_STAAU
ID DHPS_STAAU Reviewed; 267 AA.
AC O05701;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Dihydropteroate synthase {ECO:0000303|PubMed:9149138};
DE Short=DHPS {ECO:0000303|PubMed:9149138};
DE EC=2.5.1.15 {ECO:0000269|PubMed:9149138};
DE AltName: Full=Dihydropteroate pyrophosphorylase;
GN Name=folP; Synonyms=dpsA {ECO:0000303|PubMed:9149138};
OS Staphylococcus aureus.
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=1280;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF
RP APOENZYME AND IN COMPLEX WITH MANGANESE IONS AND HYDROXYMETHYLPTERIN
RP DIPHOSPHATE, SUBUNIT, FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RC STRAIN=ATCC 25923 / DSM 1104 / JCM 2413 / NBRC 14462 / NCIMB 12702 / NCTC
RC 12981 / Seattle 1945;
RX PubMed=9149138; DOI=10.1006/jmbi.1997.0944;
RA Hampele I.C., D'Arcy A., Dale G.E., Kostrewa D., Nielsen J., Oefner C.,
RA Page M.G.P., Schoenfeld H.-J., Stueber D., Then R.L.;
RT "Structure and function of the dihydropteroate synthase from Staphylococcus
RT aureus.";
RL J. Mol. Biol. 268:21-30(1997).
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:9149138}.
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:9149138};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P0AC13, ECO:0000305|PubMed:9149138};
CC Note=Magnesium is required for activity, even if it seems to interact
CC primarily with the substrate. {ECO:0000305};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=5.4 uM for 4-aminobenzoate {ECO:0000269|PubMed:9149138};
CC KM=9.3 uM for 6-hydroxymethyl-7,8-dihydropterin diphosphate
CC {ECO:0000269|PubMed:9149138};
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:9149138}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:9149138}.
CC -!- MISCELLANEOUS: Specific mutations in this gene are a major cause of
CC sulfonamide resistance in MRSA clinical isolates.
CC {ECO:0000269|PubMed:9149138}.
CC -!- SIMILARITY: Belongs to the DHPS family. {ECO:0000305}.
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DR EMBL; Z84573; CAB06539.1; -; Genomic_DNA.
DR RefSeq; WP_000167936.1; NZ_WKIW01000023.1.
DR PDB; 1AD1; X-ray; 2.20 A; A/B=2-267.
DR PDB; 1AD4; X-ray; 2.40 A; A/B=2-267.
DR PDB; 6CLU; X-ray; 1.95 A; A/B/C/D=1-267.
DR PDB; 6CLV; X-ray; 2.30 A; A/B/C/D=1-267.
DR PDBsum; 1AD1; -.
DR PDBsum; 1AD4; -.
DR PDBsum; 6CLU; -.
DR PDBsum; 6CLV; -.
DR AlphaFoldDB; O05701; -.
DR SMR; O05701; -.
DR OMA; FSIDTYH; -.
DR BRENDA; 2.5.1.15; 3352.
DR SABIO-RK; O05701; -.
DR UniPathway; UPA00077; UER00156.
DR EvolutionaryTrace; O05701; -.
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:0046677; P:response to antibiotic; 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 3D-structure; Antibiotic resistance; Folate biosynthesis; Magnesium;
KW Metal-binding; Transferase.
FT CHAIN 1..267
FT /note="Dihydropteroate synthase"
FT /id="PRO_0000168225"
FT DOMAIN 1..251
FT /note="Pterin-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00334"
FT BINDING 11
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000305|PubMed:9149138"
FT BINDING 52
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000305|PubMed:9149138,
FT ECO:0007744|PDB:1AD4"
FT BINDING 84
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000305|PubMed:9149138,
FT ECO:0007744|PDB:1AD4"
FT BINDING 103
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000305|PubMed:9149138,
FT ECO:0007744|PDB:1AD4"
FT BINDING 167
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000305|PubMed:9149138,
FT ECO:0007744|PDB:1AD4"
FT BINDING 203
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000305|PubMed:9149138,
FT ECO:0007744|PDB:1AD4"
FT BINDING 239..241
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000305|PubMed:9149138,
FT ECO:0007744|PDB:1AD4"
FT STRAND 5..10
FT /evidence="ECO:0007829|PDB:6CLU"
FT HELIX 14..16
FT /evidence="ECO:0007829|PDB:1AD1"
FT TURN 20..23
FT /evidence="ECO:0007829|PDB:1AD1"
FT HELIX 26..39
FT /evidence="ECO:0007829|PDB:6CLU"
FT STRAND 42..46
FT /evidence="ECO:0007829|PDB:6CLU"
FT STRAND 52..55
FT /evidence="ECO:0007829|PDB:6CLV"
FT HELIX 60..74
FT /evidence="ECO:0007829|PDB:6CLU"
FT STRAND 77..84
FT /evidence="ECO:0007829|PDB:6CLU"
FT HELIX 88..96
FT /evidence="ECO:0007829|PDB:6CLU"
FT STRAND 101..104
FT /evidence="ECO:0007829|PDB:6CLU"
FT TURN 105..108
FT /evidence="ECO:0007829|PDB:6CLU"
FT HELIX 114..120
FT /evidence="ECO:0007829|PDB:6CLU"
FT STRAND 124..128
FT /evidence="ECO:0007829|PDB:6CLU"
FT HELIX 139..157
FT /evidence="ECO:0007829|PDB:6CLU"
FT HELIX 161..163
FT /evidence="ECO:0007829|PDB:6CLU"
FT STRAND 164..167
FT /evidence="ECO:0007829|PDB:6CLU"
FT HELIX 176..184
FT /evidence="ECO:0007829|PDB:6CLU"
FT HELIX 186..190
FT /evidence="ECO:0007829|PDB:6CLU"
FT STRAND 196..198
FT /evidence="ECO:0007829|PDB:6CLU"
FT HELIX 204..209
FT /evidence="ECO:0007829|PDB:6CLU"
FT STRAND 210..212
FT /evidence="ECO:0007829|PDB:6CLU"
FT HELIX 217..219
FT /evidence="ECO:0007829|PDB:6CLU"
FT HELIX 220..233
FT /evidence="ECO:0007829|PDB:6CLU"
FT STRAND 237..241
FT /evidence="ECO:0007829|PDB:6CLU"
FT HELIX 243..259
FT /evidence="ECO:0007829|PDB:6CLU"
SQ SEQUENCE 267 AA; 29498 MW; F9FB01B1EAFBC275 CRC64;
MTKTKIMGIL NVTPDSFSDG GKFNNVESAV TRVKAMMDEG ADIIDVGGVS TRPGHEMITV
EEELNRVLPV VEAIVGFDVK ISVDTFRSEV AEACLKLGVD IINDQWAGLY DHRMFQVVAK
YDAEIVLMHN GNGNRDEPVV EEMLTSLLAQ AHQAKIAGIP SNKIWLDPGI GFAKTRNEEA
EVMARLDELV ATEYPVLLAT SRKRFTKEMM GYDTTPVERD EVTAATTAYG IMKGVRAVRV
HNVELNAKLA KGIDFLKENE NARHNFS
