DYRA_STAAU
ID DYRA_STAAU Reviewed; 161 AA.
AC P13955;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Dihydrofolate reductase type 1 from Tn4003;
DE EC=1.5.1.3;
GN Name=dfrA;
OS Staphylococcus aureus.
OG Plasmid pSK1.
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=1280;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TRANSPOSON=Tn4003;
RX PubMed=2548057; DOI=10.1111/j.1365-2958.1989.tb01805.x;
RA Rouch D.A., Messeroti L.J., Loo L.S.L., Jackson C.A., Skurray R.A.;
RT "Trimethoprim resistance transposon Tn4003 from Staphylococcus aureus
RT encodes genes for a dihydrofolate reductase and thymidylate synthetase
RT flanked by three copies of IS257.";
RL Mol. Microbiol. 3:161-175(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=157/4696;
RX PubMed=2365064; DOI=10.1016/0014-5793(90)81529-w;
RA Burdeska A., Ott M., Bannwarth W., Then R.L.;
RT "Identical genes for trimethoprim-resistant dihydrofolate reductase from
RT Staphylococcus aureus in Australia and central Europe.";
RL FEBS Lett. 266:159-162(1990).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH NADPH AND
RP TRIMETHOPRIM, AND MUTAGENESIS OF ALA-44 AND TYR-99.
RX PubMed=19280600; DOI=10.1002/prot.22383;
RA Heaslet H., Harris M., Fahnoe K., Sarver R., Putz H., Chang J.,
RA Subramanyam C., Barreiro G., Miller J.R.;
RT "Structural comparison of chromosomal and exogenous dihydrofolate reductase
RT from Staphylococcus aureus in complex with the potent inhibitor
RT trimethoprim.";
RL Proteins 76:706-717(2009).
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.
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 -!- MISCELLANEOUS: There are two DhfR isozymes in S.aureus, this one is
CC plasmid-encoded and is resistant to trimethoprim.
CC -!- SIMILARITY: Belongs to the dihydrofolate reductase family.
CC {ECO:0000305}.
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DR EMBL; X13290; CAA31649.1; -; Genomic_DNA.
DR EMBL; Y07536; CAA68824.1; -; Genomic_DNA.
DR PIR; S04164; S04164.
DR RefSeq; NP_877983.1; NC_005054.1.
DR RefSeq; WP_000175735.1; NZ_VTZV01000057.1.
DR RefSeq; YP_002790943.1; NC_012547.1.
DR RefSeq; YP_003813115.1; NC_014369.1.
DR RefSeq; YP_006937652.1; NC_013320.1.
DR RefSeq; YP_006937707.1; NC_013321.1.
DR RefSeq; YP_006938354.1; NC_013338.1.
DR RefSeq; YP_006938562.1; NC_013343.1.
DR PDB; 2W9S; X-ray; 1.80 A; A/B/C/D/E/F=1-161.
DR PDB; 2W9T; X-ray; 2.35 A; A/B=1-161.
DR PDBsum; 2W9S; -.
DR PDBsum; 2W9T; -.
DR AlphaFoldDB; P13955; -.
DR SMR; P13955; -.
DR BindingDB; P13955; -.
DR OMA; EECFVIG; -.
DR BRENDA; 1.5.1.3; 3352.
DR UniPathway; UPA00077; UER00158.
DR EvolutionaryTrace; P13955; -.
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:0031427; P:response to methotrexate; 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; Methotrexate resistance; NADP;
KW One-carbon metabolism; Oxidoreductase; Plasmid; Trimethoprim resistance.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250"
FT CHAIN 2..161
FT /note="Dihydrofolate reductase type 1 from Tn4003"
FT /id="PRO_0000186405"
FT DOMAIN 2..157
FT /note="DHFR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00660"
FT BINDING 6..8
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:19280600"
FT BINDING 7..8
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:19280600"
FT BINDING 15..20
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:19280600"
FT BINDING 28
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:19280600"
FT BINDING 44..47
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:19280600"
FT BINDING 58
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:19280600"
FT BINDING 63..66
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:19280600"
FT BINDING 93..98
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:19280600"
FT BINDING 112
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:19280600"
FT MUTAGEN 44
FT /note="A->G: Increases trimethoprim sensitivity; when
FT associated with F-99."
FT /evidence="ECO:0000269|PubMed:19280600"
FT MUTAGEN 99
FT /note="Y->F: Increases trimethoprim sensitivity; when
FT associated with G-44."
FT /evidence="ECO:0000269|PubMed:19280600"
FT STRAND 3..10
FT /evidence="ECO:0007829|PDB:2W9S"
FT STRAND 14..17
FT /evidence="ECO:0007829|PDB:2W9S"
FT HELIX 26..36
FT /evidence="ECO:0007829|PDB:2W9S"
FT STRAND 39..44
FT /evidence="ECO:0007829|PDB:2W9S"
FT HELIX 45..51
FT /evidence="ECO:0007829|PDB:2W9S"
FT STRAND 58..63
FT /evidence="ECO:0007829|PDB:2W9S"
FT STRAND 75..77
FT /evidence="ECO:0007829|PDB:2W9S"
FT HELIX 81..84
FT /evidence="ECO:0007829|PDB:2W9S"
FT STRAND 90..94
FT /evidence="ECO:0007829|PDB:2W9S"
FT HELIX 96..102
FT /evidence="ECO:0007829|PDB:2W9S"
FT TURN 103..105
FT /evidence="ECO:0007829|PDB:2W9S"
FT STRAND 107..116
FT /evidence="ECO:0007829|PDB:2W9S"
FT STRAND 120..123
FT /evidence="ECO:0007829|PDB:2W9S"
FT TURN 129..131
FT /evidence="ECO:0007829|PDB:2W9S"
FT STRAND 132..139
FT /evidence="ECO:0007829|PDB:2W9S"
FT STRAND 143..145
FT /evidence="ECO:0007829|PDB:2W9T"
FT STRAND 150..157
FT /evidence="ECO:0007829|PDB:2W9S"
SQ SEQUENCE 161 AA; 18461 MW; F829D6109A3AF3A0 CRC64;
MTLSIIVAHD KQRVIGYQNQ LPWHLPNDLK HIKQLTTGNT LVMARKTFNS IGKPLPNRRN
VVLTNQASFH HEGVDVINSL DEIKELSGHV FIFGGQTLYE AMIDQVDDMY ITVIDGKFQG
DTFFPPYTFE NWEVESSVEG QLDEKNTIPH TFLHLVRRKG K
