ID   DYR_NEIMB               Reviewed;         162 AA.
AC   Q9K168;
DT   29-AUG-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   03-AUG-2022, entry version 109.
DE   RecName: Full=Dihydrofolate reductase;
DE            EC=1.5.1.3;
GN   Name=folA; OrderedLocusNames=NMB0308;
OS   Neisseria meningitidis serogroup B (strain MC58).
OC   Bacteria; Proteobacteria; Betaproteobacteria; Neisseriales; Neisseriaceae;
OC   Neisseria.
OX   NCBI_TaxID=122586;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=MC58;
RX   PubMed=10710307; DOI=10.1126/science.287.5459.1809;
RA   Tettelin H., Saunders N.J., Heidelberg J.F., Jeffries A.C., Nelson K.E.,
RA   Eisen J.A., Ketchum K.A., Hood D.W., Peden J.F., Dodson R.J., Nelson W.C.,
RA   Gwinn M.L., DeBoy R.T., Peterson J.D., Hickey E.K., Haft D.H.,
RA   Salzberg S.L., White O., Fleischmann R.D., Dougherty B.A., Mason T.M.,
RA   Ciecko A., Parksey D.S., Blair E., Cittone H., Clark E.B., Cotton M.D.,
RA   Utterback T.R., Khouri H.M., Qin H., Vamathevan J.J., Gill J., Scarlato V.,
RA   Masignani V., Pizza M., Grandi G., Sun L., Smith H.O., Fraser C.M.,
RA   Moxon E.R., Rappuoli R., Venter J.C.;
RT   "Complete genome sequence of Neisseria meningitidis serogroup B strain
RT   MC58.";
RL   Science 287:1809-1815(2000).
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   -!- SIMILARITY: Belongs to the dihydrofolate reductase family.
CC       {ECO:0000305}.
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DR   EMBL; AE002098; AAF40754.1; -; Genomic_DNA.
DR   PIR; G81214; G81214.
DR   RefSeq; NP_273358.1; NC_003112.2.
DR   RefSeq; WP_002218701.1; NC_003112.2.
DR   AlphaFoldDB; Q9K168; -.
DR   SMR; Q9K168; -.
DR   STRING; 122586.NMB0308; -.
DR   PaxDb; Q9K168; -.
DR   EnsemblBacteria; AAF40754; AAF40754; NMB0308.
DR   KEGG; nme:NMB0308; -.
DR   PATRIC; fig|122586.8.peg.383; -.
DR   HOGENOM; CLU_043966_5_1_4; -.
DR   OMA; RDNQLPW; -.
DR   UniPathway; UPA00077; UER00158.
DR   Proteomes; UP000000425; Chromosome.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0004146; F:dihydrofolate reductase activity; IBA:GO_Central.
DR   GO; GO:0050661; F:NADP binding; IBA:GO_Central.
DR   GO; GO:0046452; P:dihydrofolate metabolic process; IBA:GO_Central.
DR   GO; GO:0046655; P:folic acid metabolic process; IBA:GO_Central.
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:0046654; P:tetrahydrofolate biosynthetic process; IBA:GO_Central.
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   3: Inferred from homology;
KW   NADP; One-carbon metabolism; Oxidoreductase; Reference proteome.
FT   CHAIN           1..162
FT                   /note="Dihydrofolate reductase"
FT                   /id="PRO_0000186403"
FT   DOMAIN          3..161
FT                   /note="DHFR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00660"
FT   BINDING         7..9
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         8..9
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         16..21
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         29
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         45..48
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         60
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         65..68
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         98..103
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         117
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   162 AA;  17752 MW;  B5EBB53CEABB8F62 CRC64;
     MLKITLIAAC AENLCIGAGN AMPWHIPEDF AFFKAYTLGK PVIMGRKTWE SLPVKPLPGR
     RNIVISRQAD YCAAGAETAA SLEAALALCA GAEEAVIMGG AQIYGQAMPL ATDLRITEVD
     LSVEGDAFFP AIDRTHWKEA ERTERRVSSK GTRYAFVHYL RY