ID   FOLD_FRATO              Reviewed;         282 AA.
AC   Q0BNF1;
DT   12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT   17-OCT-2006, sequence version 1.
DT   03-AUG-2022, entry version 83.
DE   RecName: Full=Bifunctional protein FolD {ECO:0000255|HAMAP-Rule:MF_01576};
DE   Includes:
DE     RecName: Full=Methylenetetrahydrofolate dehydrogenase {ECO:0000255|HAMAP-Rule:MF_01576};
DE              EC=1.5.1.5 {ECO:0000255|HAMAP-Rule:MF_01576};
DE   Includes:
DE     RecName: Full=Methenyltetrahydrofolate cyclohydrolase {ECO:0000255|HAMAP-Rule:MF_01576};
DE              EC=3.5.4.9 {ECO:0000255|HAMAP-Rule:MF_01576};
GN   Name=folD {ECO:0000255|HAMAP-Rule:MF_01576}; OrderedLocusNames=FTH_0386;
OS   Francisella tularensis subsp. holarctica (strain OSU18).
OC   Bacteria; Proteobacteria; Gammaproteobacteria; Thiotrichales;
OC   Francisellaceae; Francisella.
OX   NCBI_TaxID=393011;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=OSU18;
RX   PubMed=16980500; DOI=10.1128/jb.00506-06;
RA   Petrosino J.F., Xiang Q., Karpathy S.E., Jiang H., Yerrapragada S., Liu Y.,
RA   Gioia J., Hemphill L., Gonzalez A., Raghavan T.M., Uzman A., Fox G.E.,
RA   Highlander S., Reichard M., Morton R.J., Clinkenbeard K.D., Weinstock G.M.;
RT   "Chromosome rearrangement and diversification of Francisella tularensis
RT   revealed by the type B (OSU18) genome sequence.";
RL   J. Bacteriol. 188:6977-6985(2006).
CC   -!- FUNCTION: Catalyzes the oxidation of 5,10-methylenetetrahydrofolate to
CC       5,10-methenyltetrahydrofolate and then the hydrolysis of 5,10-
CC       methenyltetrahydrofolate to 10-formyltetrahydrofolate.
CC       {ECO:0000255|HAMAP-Rule:MF_01576}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + NADP(+) = 5,10-
CC         methenyltetrahydrofolate + NADPH; Xref=Rhea:RHEA:22812,
CC         ChEBI:CHEBI:15636, ChEBI:CHEBI:57455, ChEBI:CHEBI:57783,
CC         ChEBI:CHEBI:58349; EC=1.5.1.5; Evidence={ECO:0000255|HAMAP-
CC         Rule:MF_01576};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=5,10-methenyltetrahydrofolate + H2O = (6S)-10-
CC         formyltetrahydrofolate + H(+); Xref=Rhea:RHEA:23700,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57454,
CC         ChEBI:CHEBI:57455; EC=3.5.4.9; Evidence={ECO:0000255|HAMAP-
CC         Rule:MF_01576};
CC   -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion.
CC       {ECO:0000255|HAMAP-Rule:MF_01576}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_01576}.
CC   -!- SIMILARITY: Belongs to the tetrahydrofolate
CC       dehydrogenase/cyclohydrolase family. {ECO:0000255|HAMAP-Rule:MF_01576}.
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DR   EMBL; CP000437; ABI82383.1; -; Genomic_DNA.
DR   RefSeq; WP_003014628.1; NC_017463.1.
DR   AlphaFoldDB; Q0BNF1; -.
DR   SMR; Q0BNF1; -.
DR   KEGG; fth:FTH_0386; -.
DR   OMA; HIVGRPM; -.
DR   UniPathway; UPA00193; -.
DR   GO; GO:0004477; F:methenyltetrahydrofolate cyclohydrolase activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0004488; F:methylenetetrahydrofolate dehydrogenase (NADP+) activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0000105; P:histidine biosynthetic process; IEA:UniProtKB-KW.
DR   GO; GO:0009086; P:methionine biosynthetic process; IEA:UniProtKB-KW.
DR   GO; GO:0006164; P:purine nucleotide biosynthetic process; IEA:UniProtKB-KW.
DR   GO; GO:0035999; P:tetrahydrofolate interconversion; IEA:UniProtKB-UniPathway.
DR   CDD; cd01080; NAD_bind_m-THF_DH_Cyclohyd; 1.
DR   HAMAP; MF_01576; THF_DHG_CYH; 1.
DR   InterPro; IPR046346; Aminiacid_DH-like_N_sf.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR000672; THF_DH/CycHdrlase.
DR   InterPro; IPR020630; THF_DH/CycHdrlase_cat_dom.
DR   InterPro; IPR020867; THF_DH/CycHdrlase_CS.
DR   InterPro; IPR020631; THF_DH/CycHdrlase_NAD-bd_dom.
DR   Pfam; PF00763; THF_DHG_CYH; 1.
DR   Pfam; PF02882; THF_DHG_CYH_C; 1.
DR   PRINTS; PR00085; THFDHDRGNASE.
DR   SUPFAM; SSF51735; SSF51735; 1.
DR   SUPFAM; SSF53223; SSF53223; 1.
DR   PROSITE; PS00766; THF_DHG_CYH_1; 1.
DR   PROSITE; PS00767; THF_DHG_CYH_2; 1.
PE   3: Inferred from homology;
KW   Amino-acid biosynthesis; Histidine biosynthesis; Hydrolase;
KW   Methionine biosynthesis; Multifunctional enzyme; NADP;
KW   One-carbon metabolism; Oxidoreductase; Purine biosynthesis.
FT   CHAIN           1..282
FT                   /note="Bifunctional protein FolD"
FT                   /id="PRO_0000268351"
FT   BINDING         165..167
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01576"
FT   BINDING         231
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01576"
SQ   SEQUENCE   282 AA;  30482 MW;  0DD8E5E9F81CEF1E CRC64;
     MILIDGKSLS KDLKERLATQ VQEYKHHTAI TPKLVAIIVG NDPASKTYVA SKEKACAQVG
     IDSQVITLPE HTTESELLEL IDQLNNDSSV HAILVQLPLP AHINKNNVIY SIKPEKDVDG
     FHPTNVGRLQ LRDKKCLESC TPKGIMTMLR EYGIKTEGAY VVVVGASNVV GKPVSQLLLN
     AKATVTTCHR FTTDLKSHTT KADILIVAVG KPNFITADMV KEGAVVIDVG INHVDGKIVG
     DVDFAAVKDK VAAITPVPGG VGPMTITELL YNTFQCAQEL NR