DHPS_STRR6
ID DHPS_STRR6 Reviewed; 314 AA.
AC P59655;
DT 30-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 30-APR-2003, sequence version 1.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Dihydropteroate synthase {ECO:0000303|PubMed:10329458};
DE Short=DHPS {ECO:0000303|PubMed:10329458};
DE EC=2.5.1.15 {ECO:0000269|PubMed:10329458};
DE AltName: Full=Dihydropteroate pyrophosphorylase;
GN Name=sulA; OrderedLocusNames=spr0266;
OS Streptococcus pneumoniae (strain ATCC BAA-255 / R6).
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Streptococcaceae;
OC Streptococcus.
OX NCBI_TaxID=171101;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC BAA-255 / R6;
RX PubMed=11544234; DOI=10.1128/jb.183.19.5709-5717.2001;
RA Hoskins J., Alborn W.E. Jr., Arnold J., Blaszczak L.C., Burgett S.,
RA DeHoff B.S., Estrem S.T., Fritz L., Fu D.-J., Fuller W., Geringer C.,
RA Gilmour R., Glass J.S., Khoja H., Kraft A.R., Lagace R.E., LeBlanc D.J.,
RA Lee L.N., Lefkowitz E.J., Lu J., Matsushima P., McAhren S.M., McHenney M.,
RA McLeaster K., Mundy C.W., Nicas T.I., Norris F.H., O'Gara M., Peery R.B.,
RA Robertson G.T., Rockey P., Sun P.-M., Winkler M.E., Yang Y.,
RA Young-Bellido M., Zhao G., Zook C.A., Baltz R.H., Jaskunas S.R.,
RA Rosteck P.R. Jr., Skatrud P.L., Glass J.I.;
RT "Genome of the bacterium Streptococcus pneumoniae strain R6.";
RL J. Bacteriol. 183:5709-5717(2001).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND REACTION MECHANISM.
RX PubMed=10329458; DOI=10.1006/bbrc.1999.0695;
RA Vinnicombe H.G., Derrick J.P.;
RT "Dihydropteroate synthase from Streptococcus pneumoniae: characterization
RT of substrate binding order and sulfonamide inhibition.";
RL Biochem. Biophys. Res. Commun. 258:752-757(1999).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF APOENZYME AND IN COMPLEX WITH
RP 6-HYDROXYMETHYL-7,8-DIHYDROPTERIN MONOPHOSPHATE, SUBUNIT, AND DRUG
RP RESISTANCE.
RX PubMed=18321242; DOI=10.1042/bj20071598;
RA Levy C., Minnis D., Derrick J.P.;
RT "Dihydropteroate synthase from Streptococcus pneumoniae: structure, ligand
RT recognition and mechanism of sulfonamide resistance.";
RL Biochem. J. 412:379-388(2008).
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:10329458}.
CC -!- FUNCTION: Is the target for the sulfonamide group of antimicrobial
CC drugs. Sulfonamide drugs act as pABA analogs, they inhibit the reaction
CC by acting as alternative substrates, leading to a 'dead end' sulfa-
CC pterin product. {ECO:0000305|PubMed:10329458,
CC ECO:0000305|PubMed:18321242}.
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:10329458};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P0AC13};
CC -!- ACTIVITY REGULATION: Is potently inhibited by sulfonamides, with Ki
CC values between 25 nM and 850 nM. {ECO:0000269|PubMed:10329458}.
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:18321242}.
CC -!- MISCELLANEOUS: Reaction proceeds via an ordered binding mechanism, with
CC DHPPP binding to the enzyme first, inducing a structural change which
CC forms the pABA-binding site. {ECO:0000269|PubMed:10329458,
CC ECO:0000269|PubMed:18321242}.
CC -!- MISCELLANEOUS: One or two residue insertions within this gene are
CC responsible for sulfonamide resistance in streptococcal clinical
CC isolates. Sulfonamide-resistance mutations in the second loop region
CC have a drastic effect on pABA binding. {ECO:0000305|PubMed:18321242}.
CC -!- SIMILARITY: Belongs to the DHPS family. {ECO:0000305}.
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DR EMBL; AE007317; AAK99070.1; -; Genomic_DNA.
DR RefSeq; NP_357860.1; NC_003098.1.
DR PDB; 2VEF; X-ray; 1.80 A; A/B=1-314.
DR PDB; 2VEG; X-ray; 2.40 A; A/B=1-314.
DR PDBsum; 2VEF; -.
DR PDBsum; 2VEG; -.
DR AlphaFoldDB; P59655; -.
DR SMR; P59655; -.
DR STRING; 171101.spr0266; -.
DR EnsemblBacteria; AAK99070; AAK99070; spr0266.
DR KEGG; spr:spr0266; -.
DR PATRIC; fig|171101.6.peg.303; -.
DR eggNOG; COG0294; Bacteria.
DR HOGENOM; CLU_008023_0_2_9; -.
DR OMA; FSIDTYH; -.
DR BRENDA; 2.5.1.15; 1960.
DR UniPathway; UPA00077; UER00156.
DR EvolutionaryTrace; P59655; -.
DR Proteomes; UP000000586; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0004156; F:dihydropteroate synthase activity; IBA:GO_Central.
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; 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; Antibiotic resistance; Folate biosynthesis; Magnesium;
KW Metal-binding; Reference proteome; Transferase.
FT CHAIN 1..314
FT /note="Dihydropteroate synthase"
FT /id="PRO_0000168231"
FT DOMAIN 10..294
FT /note="Pterin-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00334"
FT BINDING 17
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:O05701"
FT BINDING 91
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000305|PubMed:18321242"
FT BINDING 110
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000305|PubMed:18321242,
FT ECO:0007744|PDB:2VEG"
FT BINDING 201
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000305|PubMed:18321242,
FT ECO:0007744|PDB:2VEG"
FT BINDING 237
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000305|PubMed:18321242,
FT ECO:0007744|PDB:2VEG"
FT BINDING 282..284
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000305|PubMed:18321242,
FT ECO:0007744|PDB:2VEG"
FT STRAND 11..17
FT /evidence="ECO:0007829|PDB:2VEF"
FT HELIX 31..44
FT /evidence="ECO:0007829|PDB:2VEF"
FT STRAND 48..53
FT /evidence="ECO:0007829|PDB:2VEF"
FT HELIX 63..83
FT /evidence="ECO:0007829|PDB:2VEF"
FT STRAND 87..91
FT /evidence="ECO:0007829|PDB:2VEF"
FT HELIX 95..103
FT /evidence="ECO:0007829|PDB:2VEF"
FT STRAND 108..111
FT /evidence="ECO:0007829|PDB:2VEF"
FT TURN 112..115
FT /evidence="ECO:0007829|PDB:2VEF"
FT HELIX 121..128
FT /evidence="ECO:0007829|PDB:2VEF"
FT STRAND 131..135
FT /evidence="ECO:0007829|PDB:2VEF"
FT HELIX 138..141
FT /evidence="ECO:0007829|PDB:2VEF"
FT TURN 146..150
FT /evidence="ECO:0007829|PDB:2VEF"
FT HELIX 166..170
FT /evidence="ECO:0007829|PDB:2VEF"
FT HELIX 173..191
FT /evidence="ECO:0007829|PDB:2VEF"
FT HELIX 195..197
FT /evidence="ECO:0007829|PDB:2VEF"
FT STRAND 198..201
FT /evidence="ECO:0007829|PDB:2VEF"
FT HELIX 210..218
FT /evidence="ECO:0007829|PDB:2VEF"
FT HELIX 220..224
FT /evidence="ECO:0007829|PDB:2VEF"
FT TURN 225..227
FT /evidence="ECO:0007829|PDB:2VEG"
FT STRAND 230..233
FT /evidence="ECO:0007829|PDB:2VEF"
FT HELIX 238..246
FT /evidence="ECO:0007829|PDB:2VEF"
FT HELIX 256..275
FT /evidence="ECO:0007829|PDB:2VEF"
FT STRAND 279..284
FT /evidence="ECO:0007829|PDB:2VEF"
FT HELIX 286..300
FT /evidence="ECO:0007829|PDB:2VEF"
SQ SEQUENCE 314 AA; 34418 MW; C7CEDD0C2EDAA061 CRC64;
MSSKANHAKT VICGIINVTP DSFSDGGQFF ALEQALQQAR KLIAEGASML DIGGESTRPG
SSYVEIEEEI QRVVPVIKAI RKESDVLISI DTWKSQVAEA ALAAGADLVN DITGLMGDEK
MPHVVAEARA QVVIMFNPVM ARPQHPSSLI FPHFGFGQAF TEEELADFET LPIEELMEAF
FERALARAAE AGIAPENILL DPGIGFGLTK KENLLLLRDL DKLHQKGYPI FLGVSRKRFV
INILEENGFE VNPETELGFR NRDTASAHVT SIAARQGVEV VRVHDVASHR MAVEIASAIR
LADEAENLDL KQYK
