ID   FOLD_PHOPO              Reviewed;         285 AA.
AC   P51696;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   02-SEP-2026, entry version 107.
DE   RecName: Full=Bifunctional protein FolD {ECO:0000255|HAMAP-Rule:MF_01576};
DE   AltName: Full=PPDC;
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};
OS   Photobacterium phosphoreum.
OC   Bacteria; Pseudomonadati; Pseudomonadota; Gammaproteobacteria; Vibrionales;
OC   Vibrionaceae; Photobacterium.
OX   NCBI_TaxID=659;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND CHARACTERIZATION.
RC   STRAIN=DSM 2167 / CIP 104260 / LMG 4231 / NCIMB 844;
RX   PubMed=8765228; DOI=10.1016/0167-4838(96)00052-0;
RA   Pawelek P.D., MacKenzie R.E.;
RT   "Methylenetetrahydrofolate dehydrogenase-cyclohydrolase from Photobacterium
RT   phosphoreum shares properties with a mammalian mitochondrial homologue.";
RL   Biochim. Biophys. Acta 1296:47-54(1996).
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   -!- CATALYTIC ACTIVITY:
CC       Reaction=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + NADP(+) = (6R)-
CC         5,10-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=(6R)-5,10-methenyltetrahydrofolate + H2O = (6R)-10-
CC         formyltetrahydrofolate + H(+); Xref=Rhea:RHEA:23700,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57455,
CC         ChEBI:CHEBI:195366; EC=3.5.4.9; Evidence={ECO:0000255|HAMAP-
CC         Rule:MF_01576};
CC   -!- ACTIVITY REGULATION: The NAD(+)-dependent dehydrogenase is activated by
CC       inorganic phosphate.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.2 mM for NADP(+);
CC         KM=4.76 mM for NAD(+);
CC   -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion.
CC       {ECO:0000255|HAMAP-Rule:MF_01576}.
CC   -!- SUBUNIT: Homodimer.
CC   -!- SIMILARITY: Belongs to the tetrahydrofolate
CC       dehydrogenase/cyclohydrolase family. {ECO:0000255|HAMAP-Rule:MF_01576}.
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DR   EMBL; U34207; AAA98507.1; -; Genomic_DNA.
DR   PIR; S71924; S71924.
DR   AlphaFoldDB; P51696; -.
DR   SMR; P51696; -.
DR   STRING; 659.AYY26_02810; -.
DR   SABIO-RK; P51696; -.
DR   UniPathway; UPA00193; -.
DR   GO; GO:0005829; C:cytosol; IEA:TreeGrafter.
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:0035999; P:tetrahydrofolate interconversion; IEA:UniProtKB-UniRule.
DR   CDD; cd01080; NAD_bind_m-THF_DH_Cyclohyd; 1.
DR   FunFam; 3.40.50.10860:FF:000001; Bifunctional protein FolD; 1.
DR   FunFam; 3.40.50.720:FF:000006; Bifunctional protein FolD; 1.
DR   Gene3D; 3.40.50.10860; Leucine Dehydrogenase, chain A, domain 1; 1.
DR   Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR   HAMAP; MF_01576; THF_DHG_CYH; 1.
DR   InterPro; IPR046346; Aminoacid_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   NCBIfam; NF008058; PRK10792.1; 1.
DR   NCBIfam; NF010783; PRK14186.1; 1.
DR   PANTHER; PTHR48099:SF5; C-1-TETRAHYDROFOLATE SYNTHASE, CYTOPLASMIC; 1.
DR   PANTHER; PTHR48099; C-1-TETRAHYDROFOLATE SYNTHASE, CYTOPLASMIC-RELATED; 1.
DR   Pfam; PF00763; THF_DHG_CYH; 1.
DR   Pfam; PF02882; THF_DHG_CYH_C; 1.
DR   PRINTS; PR00085; THFDHDRGNASE.
DR   SUPFAM; SSF53223; Aminoacid dehydrogenase-like, N-terminal domain; 1.
DR   SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
DR   PROSITE; PS00766; THF_DHG_CYH_1; 1.
DR   PROSITE; PS00767; THF_DHG_CYH_2; 1.
PE   1: Evidence at protein level;
KW   Amino-acid biosynthesis; Histidine biosynthesis; Hydrolase;
KW   Methionine biosynthesis; Multifunctional enzyme; NADP;
KW   One-carbon metabolism; Oxidoreductase; Purine biosynthesis.
FT   CHAIN           1..285
FT                   /note="Bifunctional protein FolD"
FT                   /id="PRO_0000199312"
FT   BINDING         166..168
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01576"
FT   BINDING         232
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01576"
SQ   SEQUENCE   285 AA;  30776 MW;  9EB1FC954EAA4396 CRC64;
     MSAQIIDGKI ISQTVRQEVA ARVKARTDAG LRAPGLAVVL VGQDPASQIY VGSKRKACEE
     VGFISKSFDL PSSASEQQLL DLIDELNQDP TMDGILVQLP LPAGMDCTRI LERIDPEKDV
     DGFHPYNVGR LSQRIPKLRS CTPKGIITLL ERYNIEVRGK HAVIVGASNI VGRPMTLELL
     LAGATTTTCH RFTQDLEGHI RQADILVVAV GKPNFIPGGW IKEGATVIDV GINRLENGKL
     CGDVEFDVAC QRAKYITPVP GGVGPMTVAS LIENTLLACE QYHSA
//