DHPS_ECOLI
ID DHPS_ECOLI Reviewed; 282 AA.
AC P0AC13; P26282; P78110; Q2M935;
DT 08-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 08-NOV-2005, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Dihydropteroate synthase {ECO:0000303|PubMed:1522070};
DE Short=DHPS {ECO:0000303|PubMed:1522070};
DE EC=2.5.1.15 {ECO:0000269|PubMed:368012};
DE AltName: Full=Dihydropteroate pyrophosphorylase;
GN Name=folP; Synonyms=dhpS; OrderedLocusNames=b3177, JW3144;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=C-167;
RX PubMed=8304179; DOI=10.1007/978-1-4615-2960-6_113;
RA Swedberg G., Fermer C., Skoeld O.;
RT "Point mutations in the dihydropteroate synthase gene causing sulfonamide
RT resistance.";
RL Adv. Exp. Med. Biol. 338:555-558(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=1522070; DOI=10.1128/jb.174.18.5961-5970.1992;
RA Dallas W.S., Gowen J.E., Ray P.H., Cox M.J., Dev I.K.;
RT "Cloning, sequencing, and enhanced expression of the dihydropteroate
RT synthase gene of Escherichia coli MC4100.";
RL J. Bacteriol. 174:5961-5970(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12;
RA Wang R., Kushner S.R.;
RL Submitted (SEP-1993) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [6]
RP PROTEIN SEQUENCE OF 1-28.
RC STRAIN=K12 / MC4100 / ATCC 35695 / DSM 6574;
RX PubMed=1657875; DOI=10.1128/jb.173.21.7029-7032.1991;
RA Talarico T.L., Dev I.K., Dallas W.S., Ferone R., Ray P.H.;
RT "Purification and partial characterization of 7,8-dihydro-6-
RT hydroxymethylpterin-pyrophosphokinase and 7,8-dihydropteroate synthase from
RT Escherichia coli MC4100.";
RL J. Bacteriol. 173:7029-7032(1991).
RN [7]
RP CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RX PubMed=4304228; DOI=10.1016/s0021-9258(18)91799-0;
RA Richey D.P., Brown G.M.;
RT "The biosynthesis of folic acid. IX. Purification and properties of the
RT enzymes required for the formation of dihydropteroic acid.";
RL J. Biol. Chem. 244:1582-1592(1969).
RN [8]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RC STRAIN=C-167;
RX PubMed=368012; DOI=10.1128/jb.137.1.129-136.1979;
RA Swedberg G., Castensson S., Skold O.;
RT "Characterization of mutationally altered dihydropteroate synthase and its
RT ability to form a sulfonamide-containing dihydrofolate analog.";
RL J. Bacteriol. 137:129-136(1979).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEXES WITH SUBSTRATE;
RP SULFANILAMIDE AND SUBSTRATE ANALOG, AND SUBUNIT.
RX PubMed=9187658; DOI=10.1038/nsb0697-490;
RA Achari A., Somers D.O., Champness J.N., Bryant P.K., Rosemond J.,
RA Stammers D.K.;
RT "Crystal structure of the anti-bacterial sulfonamide drug target
RT dihydropteroate synthase.";
RL Nat. Struct. Biol. 4:490-497(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 (H2Pte), the immediate precursor of folate derivatives.
CC {ECO:0000269|PubMed:368012}.
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; Evidence={ECO:0000269|PubMed:368012,
CC ECO:0000269|PubMed:4304228};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:4304228};
CC Note=Magnesium is required for activity, even if it seems to interact
CC primarily with the substrate. {ECO:0000269|PubMed:4304228,
CC ECO:0000305};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.5 uM for 4-aminobenzoate {ECO:0000269|PubMed:4304228};
CC pH dependence:
CC Optimum pH is 8.5. {ECO:0000269|PubMed:4304228};
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:0000269|PubMed:4304228,
CC ECO:0000269|PubMed:9187658}.
CC -!- SIMILARITY: Belongs to the DHPS family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA57978.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; X68776; CAA48676.1; -; Genomic_DNA.
DR EMBL; X68777; CAA48677.1; -; Genomic_DNA.
DR EMBL; L06494; AAA23804.1; -; Genomic_DNA.
DR EMBL; L12968; AAA16123.1; -; Unassigned_DNA.
DR EMBL; U01376; AAA97509.1; -; Genomic_DNA.
DR EMBL; U18997; AAA57978.1; ALT_INIT; Genomic_DNA.
DR EMBL; U00096; AAC76209.2; -; Genomic_DNA.
DR EMBL; AP009048; BAE77221.1; -; Genomic_DNA.
DR PIR; A43326; A43326.
DR RefSeq; NP_417644.4; NC_000913.3.
DR RefSeq; WP_000764731.1; NZ_STEB01000012.1.
DR PDB; 1AJ0; X-ray; 2.00 A; A=1-282.
DR PDB; 1AJ2; X-ray; 2.00 A; A=1-282.
DR PDB; 1AJZ; X-ray; 2.00 A; A=1-282.
DR PDBsum; 1AJ0; -.
DR PDBsum; 1AJ2; -.
DR PDBsum; 1AJZ; -.
DR AlphaFoldDB; P0AC13; -.
DR SMR; P0AC13; -.
DR BioGRID; 4261486; 17.
DR DIP; DIP-47922N; -.
DR IntAct; P0AC13; 1.
DR STRING; 511145.b3177; -.
DR BindingDB; P0AC13; -.
DR ChEMBL; CHEMBL2364668; -.
DR ChEMBL; CHEMBL4032; -.
DR DrugBank; DB14033; Acetyl sulfisoxazole.
DR DrugBank; DB00634; Sulfacetamide.
DR DrugBank; DB01298; Sulfacytine.
DR DrugBank; DB01581; Sulfamerazine.
DR DrugBank; DB06821; Sulfameter.
DR DrugBank; DB01582; Sulfamethazine.
DR DrugBank; DB00576; Sulfamethizole.
DR DrugBank; DB01015; Sulfamethoxazole.
DR DrugBank; DB00259; Sulfanilamide.
DR DrugBank; DB06729; Sulfaphenazole.
DR DrugBank; DB00263; Sulfisoxazole.
DR DrugCentral; P0AC13; -.
DR jPOST; P0AC13; -.
DR PaxDb; P0AC13; -.
DR PRIDE; P0AC13; -.
DR EnsemblBacteria; AAC76209; AAC76209; b3177.
DR EnsemblBacteria; BAE77221; BAE77221; BAE77221.
DR GeneID; 66672921; -.
DR GeneID; 947691; -.
DR KEGG; ecj:JW3144; -.
DR KEGG; eco:b3177; -.
DR PATRIC; fig|1411691.4.peg.3555; -.
DR EchoBASE; EB4304; -.
DR eggNOG; COG0294; Bacteria.
DR HOGENOM; CLU_008023_0_3_6; -.
DR InParanoid; P0AC13; -.
DR OMA; FSIDTYH; -.
DR PhylomeDB; P0AC13; -.
DR BioCyc; EcoCyc:H2PTEROATESYNTH-MON; -.
DR BioCyc; MetaCyc:H2PTEROATESYNTH-MON; -.
DR BRENDA; 2.5.1.15; 2026.
DR SABIO-RK; P0AC13; -.
DR UniPathway; UPA00077; UER00156.
DR EvolutionaryTrace; P0AC13; -.
DR PRO; PR:P0AC13; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IDA:EcoCyc.
DR GO; GO:0005829; C:cytosol; IDA:EcoCyc.
DR GO; GO:0004156; F:dihydropteroate synthase activity; IDA:EcoliWiki.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0046656; P:folic acid biosynthetic process; IMP:EcoCyc.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IMP:EcoliWiki.
DR GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IBA:GO_Central.
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; Direct protein sequencing; Folate biosynthesis; Magnesium;
KW Metal-binding; Reference proteome; Transferase.
FT CHAIN 1..282
FT /note="Dihydropteroate synthase"
FT /id="PRO_0000168207"
FT DOMAIN 15..267
FT /note="Pterin-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00334"
FT BINDING 22
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P9WND1"
FT BINDING 62
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000305|PubMed:9187658,
FT ECO:0007744|PDB:1AJ2"
FT BINDING 96
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000305|PubMed:9187658,
FT ECO:0007744|PDB:1AJ2"
FT BINDING 115
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000305|PubMed:9187658,
FT ECO:0007744|PDB:1AJ2"
FT BINDING 185
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000305|PubMed:9187658,
FT ECO:0007744|PDB:1AJ2"
FT BINDING 221
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000305|PubMed:9187658,
FT ECO:0007744|PDB:1AJ2"
FT BINDING 255..257
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000305|PubMed:9187658,
FT ECO:0007744|PDB:1AJ2"
FT VARIANT 28
FT /note="F -> I (in TS20; resistant to sulfonamide and
FT temperature-sensitive)"
FT CONFLICT 6
FT /note="Q -> E (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 77
FT /note="R -> A (in Ref. 3; AAA97509)"
FT /evidence="ECO:0000305"
FT STRAND 2..5
FT /evidence="ECO:0007829|PDB:1AJ0"
FT STRAND 8..11
FT /evidence="ECO:0007829|PDB:1AJ0"
FT STRAND 16..22
FT /evidence="ECO:0007829|PDB:1AJ0"
FT TURN 25..27
FT /evidence="ECO:0007829|PDB:1AJ0"
FT HELIX 29..33
FT /evidence="ECO:0007829|PDB:1AJ0"
FT HELIX 36..50
FT /evidence="ECO:0007829|PDB:1AJ0"
FT STRAND 53..60
FT /evidence="ECO:0007829|PDB:1AJ0"
FT HELIX 71..88
FT /evidence="ECO:0007829|PDB:1AJ0"
FT STRAND 92..96
FT /evidence="ECO:0007829|PDB:1AJ0"
FT HELIX 100..108
FT /evidence="ECO:0007829|PDB:1AJ0"
FT STRAND 113..116
FT /evidence="ECO:0007829|PDB:1AJ0"
FT TURN 117..120
FT /evidence="ECO:0007829|PDB:1AJ0"
FT HELIX 125..132
FT /evidence="ECO:0007829|PDB:1AJ0"
FT STRAND 136..139
FT /evidence="ECO:0007829|PDB:1AJ0"
FT HELIX 157..174
FT /evidence="ECO:0007829|PDB:1AJ0"
FT HELIX 179..181
FT /evidence="ECO:0007829|PDB:1AJ0"
FT STRAND 182..185
FT /evidence="ECO:0007829|PDB:1AJ0"
FT HELIX 194..202
FT /evidence="ECO:0007829|PDB:1AJ0"
FT HELIX 204..210
FT /evidence="ECO:0007829|PDB:1AJ0"
FT STRAND 214..216
FT /evidence="ECO:0007829|PDB:1AJ0"
FT HELIX 222..228
FT /evidence="ECO:0007829|PDB:1AJ0"
FT HELIX 232..234
FT /evidence="ECO:0007829|PDB:1AJ0"
FT HELIX 236..248
FT /evidence="ECO:0007829|PDB:1AJ0"
FT STRAND 252..257
FT /evidence="ECO:0007829|PDB:1AJ0"
FT HELIX 259..275
FT /evidence="ECO:0007829|PDB:1AJ0"
SQ SEQUENCE 282 AA; 30615 MW; 6230C8883796F59E CRC64;
MKLFAQGTSL DLSHPHVMGI LNVTPDSFSD GGTHNSLIDA VKHANLMINA GATIIDVGGE
STRPGAAEVS VEEELQRVIP VVEAIAQRFE VWISVDTSKP EVIRESAKVG AHIINDIRSL
SEPGALEAAA ETGLPVCLMH MQGNPKTMQE APKYDDVFAE VNRYFIEQIA RCEQAGIAKE
KLLLDPGFGF GKNLSHNYSL LARLAEFHHF NLPLLVGMSR KSMIGQLLNV GPSERLSGSL
ACAVIAAMQG AHIIRVHDVK ETVEAMRVVE ATLSAKENKR YE
