ID   FOLM_ECOLI              Reviewed;         240 AA.
AC   P0AFS3; P52109; P77386;
DT   20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT   20-DEC-2005, sequence version 1.
DT   24-JAN-2024, entry version 124.
DE   RecName: Full=Dihydromonapterin reductase {ECO:0000303|PubMed:19897652};
DE            Short=H(2)-MPt reductase {ECO:0000303|PubMed:19897652};
DE            EC=1.5.1.50 {ECO:0000269|PubMed:19897652};
DE   AltName: Full=Dihydrofolate reductase {ECO:0000303|PubMed:14617668};
DE            Short=DHFR;
DE            EC=1.5.1.3 {ECO:0000269|PubMed:14617668};
GN   Name=folM {ECO:0000303|PubMed:14617668}; Synonyms=ydgB;
GN   OrderedLocusNames=b1606, JW1598;
OS   Escherichia coli (strain K12).
OC   Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales;
OC   Enterobacteriaceae; Escherichia.
OX   NCBI_TaxID=83333;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX   PubMed=9097039; DOI=10.1093/dnares/3.6.363;
RA   Aiba H., Baba T., Fujita K., Hayashi K., Inada T., Isono K., Itoh T.,
RA   Kasai H., Kashimoto K., Kimura S., Kitakawa M., Kitagawa M., Makino K.,
RA   Miki T., Mizobuchi K., Mori H., Mori T., Motomura K., Nakade S.,
RA   Nakamura Y., Nashimoto H., Nishio Y., Oshima T., Saito N., Sampei G.,
RA   Seki Y., Sivasundaram S., Tagami H., Takeda J., Takemoto K., Takeuchi Y.,
RA   Wada C., Yamamoto Y., Horiuchi T.;
RT   "A 570-kb DNA sequence of the Escherichia coli K-12 genome corresponding to
RT   the 28.0-40.1 min region on the linkage map.";
RL   DNA Res. 3:363-377(1996).
RN   [2]
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   [3]
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   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 179-240.
RC   STRAIN=K12;
RA   Kuempel P.L.;
RL   Submitted (NOV-1995) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC   STRAIN=K12 / MG1655 / ATCC 47076;
RX   PubMed=14617668; DOI=10.1128/jb.185.23.7015-7018.2003;
RA   Giladi M., Altman-Price N., Levin I., Levy L., Mevarech M.;
RT   "FolM, a new chromosomally encoded dihydrofolate reductase in Escherichia
RT   coli.";
RL   J. Bacteriol. 185:7015-7018(2003).
RN   [6]
RP   FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC   STRAIN=K12 / MG1655 / ATCC 47076;
RX   PubMed=19897652; DOI=10.1128/jb.01198-09;
RA   Pribat A., Blaby I.K., Lara-Nunez A., Gregory J.F., de Crecy-Lagard V.,
RA   Hanson A.D.;
RT   "FolX and FolM are essential for tetrahydromonapterin synthesis in
RT   Escherichia coli and Pseudomonas aeruginosa.";
RL   J. Bacteriol. 192:475-482(2010).
CC   -!- FUNCTION: Catalyzes the reduction of dihydromonapterin to
CC       tetrahydromonapterin. Also has lower activity with dihydrofolate.
CC       {ECO:0000269|PubMed:19897652}.
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;
CC         Evidence={ECO:0000269|PubMed:14617668};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=7,8-dihydromonapterin + H(+) + NADPH = 5,6,7,8-
CC         tetrahydromonapterin + NADP(+); Xref=Rhea:RHEA:34847,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC         ChEBI:CHEBI:71175, ChEBI:CHEBI:71177; EC=1.5.1.50;
CC         Evidence={ECO:0000269|PubMed:19897652};
CC   -!- ACTIVITY REGULATION: Inhibited by methotrexate.
CC       {ECO:0000269|PubMed:14617668}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=9.5 uM for 7,8-dihydrofolate (at pH 6.0)
CC         {ECO:0000269|PubMed:14617668};
CC         KM=147 uM for 7,8-dihydromonapterin (at pH 6.0)
CC         {ECO:0000269|PubMed:19897652};
CC         KM=1.9 uM for NADPH (at pH 6.0) {ECO:0000269|PubMed:14617668};
CC         Vmax=0.083 umol/min/mg enzyme with 7,8-dihydrofolate as substrate
CC         {ECO:0000269|PubMed:14617668};
CC         Vmax=5.99 umol/min/mg enzyme with 7,8-dihydromoapterin as substrate
CC         {ECO:0000269|PubMed:19897652};
CC       pH dependence:
CC         Optimum pH is 4.7. {ECO:0000269|PubMed:14617668};
CC   -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC       family. FolM subfamily. {ECO:0000305}.
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DR   EMBL; U00096; AAC74678.1; -; Genomic_DNA.
DR   EMBL; AP009048; BAA15344.1; -; Genomic_DNA.
DR   EMBL; U41101; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   PIR; H64916; H64916.
DR   RefSeq; NP_416123.1; NC_000913.3.
DR   RefSeq; WP_000520804.1; NZ_SSZK01000001.1.
DR   AlphaFoldDB; P0AFS3; -.
DR   SMR; P0AFS3; -.
DR   BioGRID; 4262123; 119.
DR   DIP; DIP-47981N; -.
DR   IntAct; P0AFS3; 5.
DR   STRING; 511145.b1606; -.
DR   jPOST; P0AFS3; -.
DR   PaxDb; 511145-b1606; -.
DR   EnsemblBacteria; AAC74678; AAC74678; b1606.
DR   GeneID; 949096; -.
DR   KEGG; ecj:JW1598; -.
DR   KEGG; eco:b1606; -.
DR   PATRIC; fig|1411691.4.peg.656; -.
DR   EchoBASE; EB2981; -.
DR   eggNOG; COG1028; Bacteria.
DR   HOGENOM; CLU_010194_1_3_6; -.
DR   InParanoid; P0AFS3; -.
DR   OMA; QIHVHAP; -.
DR   OrthoDB; 9793499at2; -.
DR   PhylomeDB; P0AFS3; -.
DR   BioCyc; EcoCyc:G6862-MONOMER; -.
DR   BioCyc; MetaCyc:G6862-MONOMER; -.
DR   BRENDA; 1.5.1.50; 2026.
DR   SABIO-RK; P0AFS3; -.
DR   PRO; PR:P0AFS3; -.
DR   Proteomes; UP000000318; Chromosome.
DR   Proteomes; UP000000625; Chromosome.
DR   GO; GO:0004146; F:dihydrofolate reductase activity; IDA:EcoCyc.
DR   GO; GO:0071172; F:dihydromonapterin reductase activity; IDA:EcoCyc.
DR   GO; GO:0042802; F:identical protein binding; IDA:EcoCyc.
DR   GO; GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0051289; P:protein homotetramerization; IDA:EcoCyc.
DR   GO; GO:0042559; P:pteridine-containing compound biosynthetic process; IMP:EcoCyc.
DR   CDD; cd05357; PR_SDR_c; 1.
DR   Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR   InterPro; IPR002347; SDR_fam.
DR   PANTHER; PTHR43639:SF6; DIHYDROMONAPTERIN REDUCTASE; 1.
DR   PANTHER; PTHR43639; OXIDOREDUCTASE, SHORT-CHAIN DEHYDROGENASE/REDUCTASE FAMILY (AFU_ORTHOLOGUE AFUA_5G02870); 1.
DR   Pfam; PF13561; adh_short_C2; 1.
DR   PRINTS; PR00081; GDHRDH.
DR   SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
DR   PROSITE; PS00061; ADH_SHORT; 1.
PE   1: Evidence at protein level;
KW   NADP; One-carbon metabolism; Oxidoreductase; Reference proteome.
FT   CHAIN           1..240
FT                   /note="Dihydromonapterin reductase"
FT                   /id="PRO_0000054833"
FT   ACT_SITE        152
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT   CONFLICT        210
FT                   /note="E -> Q (in Ref. 4)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   240 AA;  26348 MW;  73B942EE144E2CC3 CRC64;
     MGKTQPLPIL ITGGGRRIGL ALAWHFINQK QPVIVSYRTH YPAIDGLINA GAQCIQADFS
     TNDGVMAFAD EVLKSTHGLR AILHNASAWM AEKPGAPLAD VLACMMQIHV NTPYLLNHAL
     ERLLRGHGHA ASDIIHFTDY VVERGSDKHI AYAASKAALD NMTRSFARKL APEVKVNSIA
     PSLILFNEHD DAEYRQQALN KSLMKTAPGE KEVIDLVDYL LTSCFVTGRS FPLDGGRHLR
//