DYR_STRPN
ID DYR_STRPN Reviewed; 168 AA.
AC Q54801; O08440; O08441; O08442; O08443; Q54973;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 26-SEP-2001, sequence version 2.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Dihydrofolate reductase;
DE EC=1.5.1.3;
GN Name=dhfR; Synonyms=dfr; OrderedLocusNames=SP_1571;
OS Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4).
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Streptococcaceae;
OC Streptococcus.
OX NCBI_TaxID=170187;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 49619 / 262 / CIP 104340 / Serotype 19F, and
RC Trimethoprim resistant 1/1 Johannesburg 1993;
RA Caspers P.;
RL Submitted (JUL-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=30, 56, 92, and Trimethoprim resistant 21;
RX PubMed=9371341; DOI=10.1128/aac.41.11.2406;
RA Adrian P.V., Klugman K.P.;
RT "Mutations in the dihydrofolate reductase gene of trimethoprim-resistant
RT isolates of Streptococcus pneumoniae.";
RL Antimicrob. Agents Chemother. 41:2406-2413(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC BAA-334 / TIGR4;
RX PubMed=11463916; DOI=10.1126/science.1061217;
RA Tettelin H., Nelson K.E., Paulsen I.T., Eisen J.A., Read T.D.,
RA Peterson S.N., Heidelberg J.F., DeBoy R.T., Haft D.H., Dodson R.J.,
RA Durkin A.S., Gwinn M.L., Kolonay J.F., Nelson W.C., Peterson J.D.,
RA Umayam L.A., White O., Salzberg S.L., Lewis M.R., Radune D.,
RA Holtzapple E.K., Khouri H.M., Wolf A.M., Utterback T.R., Hansen C.L.,
RA McDonald L.A., Feldblyum T.V., Angiuoli S.V., Dickinson T., Hickey E.K.,
RA Holt I.E., Loftus B.J., Yang F., Smith H.O., Venter J.C., Dougherty B.A.,
RA Morrison D.A., Hollingshead S.K., Fraser C.M.;
RT "Complete genome sequence of a virulent isolate of Streptococcus
RT pneumoniae.";
RL Science 293:498-506(2001).
CC -!- FUNCTION: Key enzyme in folate metabolism. Catalyzes an essential
CC reaction for de novo glycine and purine synthesis, and for DNA
CC precursor synthesis (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate +
CC H(+) + NADPH; Xref=Rhea:RHEA:15009, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57451, ChEBI:CHEBI:57453, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=1.5.1.3; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU00660};
CC -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-
CC tetrahydrofolate from 7,8-dihydrofolate: step 1/1.
CC -!- INTERACTION:
CC Q54801; Q97SJ0: SP_0371; NbExp=4; IntAct=EBI-6473264, EBI-6473258;
CC -!- MISCELLANEOUS: Strains 1/1, 21, 30, 56 and 92 are trimethoprim
CC resistant.
CC -!- SIMILARITY: Belongs to the dihydrofolate reductase family.
CC {ECO:0000305}.
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DR EMBL; Z74777; CAA99035.1; -; Genomic_DNA.
DR EMBL; Z74778; CAA99036.1; -; Genomic_DNA.
DR EMBL; Z84378; CAB06418.1; -; Genomic_DNA.
DR EMBL; Z84379; CAB06419.1; -; Genomic_DNA.
DR EMBL; Z84380; CAB06420.1; -; Genomic_DNA.
DR EMBL; Z84381; CAB06421.1; -; Genomic_DNA.
DR EMBL; AE005672; AAK75658.1; -; Genomic_DNA.
DR PIR; A95183; A95183.
DR RefSeq; WP_000162484.1; NZ_AKVY01000001.1.
DR PDB; 3IX9; X-ray; 1.95 A; A/B=1-168.
DR PDBsum; 3IX9; -.
DR AlphaFoldDB; Q54801; -.
DR SMR; Q54801; -.
DR IntAct; Q54801; 1.
DR STRING; 170187.SP_1571; -.
DR BindingDB; Q54801; -.
DR ChEMBL; CHEMBL4296314; -.
DR EnsemblBacteria; AAK75658; AAK75658; SP_1571.
DR KEGG; spn:SP_1571; -.
DR eggNOG; COG0262; Bacteria.
DR OMA; RDNQLPW; -.
DR PhylomeDB; Q54801; -.
DR BioCyc; SPNE170187:G1FZB-1590-MON; -.
DR BRENDA; 1.5.1.3; 1960.
DR UniPathway; UPA00077; UER00158.
DR EvolutionaryTrace; Q54801; -.
DR Proteomes; UP000000585; Chromosome.
DR GO; GO:0004146; F:dihydrofolate reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR GO; GO:0006545; P:glycine biosynthetic process; IEA:InterPro.
DR GO; GO:0006730; P:one-carbon metabolic 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; cd00209; DHFR; 1.
DR Gene3D; 3.40.430.10; -; 1.
DR InterPro; IPR012259; DHFR.
DR InterPro; IPR024072; DHFR-like_dom_sf.
DR InterPro; IPR017925; DHFR_CS.
DR InterPro; IPR001796; DHFR_dom.
DR PANTHER; PTHR48069; PTHR48069; 1.
DR Pfam; PF00186; DHFR_1; 1.
DR PIRSF; PIRSF000194; DHFR; 1.
DR SUPFAM; SSF53597; SSF53597; 1.
DR PROSITE; PS00075; DHFR_1; 1.
DR PROSITE; PS51330; DHFR_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic resistance; NADP; One-carbon metabolism;
KW Oxidoreductase; Trimethoprim resistance.
FT CHAIN 1..168
FT /note="Dihydrofolate reductase"
FT /id="PRO_0000186417"
FT DOMAIN 4..165
FT /note="DHFR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00660"
FT BINDING 8..10
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 9..10
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 17..22
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 30
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 46..49
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 61
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 66..69
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 83
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 100..105
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 119
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT VARIANT 14
FT /note="E -> D (in strain: 21)"
FT VARIANT 20
FT /note="E -> D (in strain: 21, 30 and 1/1)"
FT VARIANT 60
FT /note="K -> Q (in strain: 30, 56 and 1/1)"
FT VARIANT 65
FT /note="I -> V (in strain: 92)"
FT VARIANT 70
FT /note="P -> S (in strain: 21, 56 and 1/1)"
FT VARIANT 74
FT /note="I -> L (in strain: 21)"
FT VARIANT 77..78
FT /note="VA -> AV (in strain: 30)"
FT VARIANT 81
FT /note="Q -> H (in strain: 21, 56 and 1/1)"
FT VARIANT 91
FT /note="Q -> H (in strain: 21)"
FT VARIANT 92
FT /note="A -> D (in strain: ATCC 49619)"
FT VARIANT 94
FT /note="E -> D (in strain: 21)"
FT VARIANT 100
FT /note="I -> L (in strain: 21, 30, 56 and 1/1)"
FT VARIANT 111
FT /note="P -> S (in strain: 56 and 1/1)"
FT VARIANT 135
FT /note="L -> F (in strain: 21, 30, 56 and 1/1)"
FT VARIANT 141
FT /note="E -> D (in strain: 56)"
FT VARIANT 147..149
FT /note="FYA -> SYT (in strain: 21)"
FT STRAND 5..11
FT /evidence="ECO:0007829|PDB:3IX9"
FT STRAND 16..19
FT /evidence="ECO:0007829|PDB:3IX9"
FT HELIX 28..38
FT /evidence="ECO:0007829|PDB:3IX9"
FT STRAND 41..46
FT /evidence="ECO:0007829|PDB:3IX9"
FT HELIX 47..52
FT /evidence="ECO:0007829|PDB:3IX9"
FT TURN 53..55
FT /evidence="ECO:0007829|PDB:3IX9"
FT STRAND 62..66
FT /evidence="ECO:0007829|PDB:3IX9"
FT STRAND 75..82
FT /evidence="ECO:0007829|PDB:3IX9"
FT HELIX 83..91
FT /evidence="ECO:0007829|PDB:3IX9"
FT STRAND 97..101
FT /evidence="ECO:0007829|PDB:3IX9"
FT HELIX 103..109
FT /evidence="ECO:0007829|PDB:3IX9"
FT HELIX 110..112
FT /evidence="ECO:0007829|PDB:3IX9"
FT STRAND 114..123
FT /evidence="ECO:0007829|PDB:3IX9"
FT STRAND 128..130
FT /evidence="ECO:0007829|PDB:3IX9"
FT HELIX 137..139
FT /evidence="ECO:0007829|PDB:3IX9"
FT STRAND 140..148
FT /evidence="ECO:0007829|PDB:3IX9"
FT STRAND 158..165
FT /evidence="ECO:0007829|PDB:3IX9"
SQ SEQUENCE 168 AA; 19703 MW; 4C3887E290B6303E CRC64;
MTKKIVAIWA QDEEGVIGKE NRLPWHLPAE LQHFKETTLN HAILMGRVTF DGMGRRLLPK
RETLILTRNP EEKIDGVATF QDVQSVLDWY QAQEKNLYII GGKQIFQAFE PYLDEVIVTH
IHARVEGDTY FPEELDLSLF ETVSSKFYAK DEKNPYDFTI QYRKRKEV
