ID   FOLD_BRAHW              Reviewed;         281 AA.
AC   C0R292;
DT   28-JUL-2009, integrated into UniProtKB/Swiss-Prot.
DT   05-MAY-2009, sequence version 1.
DT   03-AUG-2022, entry version 75.
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=BHWA1_01765;
OS   Brachyspira hyodysenteriae (strain ATCC 49526 / WA1).
OC   Bacteria; Spirochaetes; Brachyspirales; Brachyspiraceae; Brachyspira.
OX   NCBI_TaxID=565034;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 49526 / WA1;
RX   PubMed=19262690; DOI=10.1371/journal.pone.0004641;
RA   Bellgard M.I., Wanchanthuek P., La T., Ryan K., Moolhuijzen P.,
RA   Albertyn Z., Shaban B., Motro Y., Dunn D.S., Schibeci D., Hunter A.,
RA   Barrero R., Phillips N.D., Hampson D.J.;
RT   "Genome sequence of the pathogenic intestinal spirochete Brachyspira
RT   hyodysenteriae reveals adaptations to its lifestyle in the porcine large
RT   intestine.";
RL   PLoS ONE 4:E4641-E4641(2009).
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; CP001357; ACN84230.1; -; Genomic_DNA.
DR   RefSeq; WP_012671270.1; NC_012225.1.
DR   AlphaFoldDB; C0R292; -.
DR   SMR; C0R292; -.
DR   STRING; 565034.BHWA1_01765; -.
DR   EnsemblBacteria; ACN84230; ACN84230; BHWA1_01765.
DR   GeneID; 63962862; -.
DR   KEGG; bhy:BHWA1_01765; -.
DR   eggNOG; COG0190; Bacteria.
DR   HOGENOM; CLU_034045_2_1_12; -.
DR   OMA; HIVGRPM; -.
DR   UniPathway; UPA00193; -.
DR   Proteomes; UP000001803; Chromosome.
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; 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.
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..281
FT                   /note="Bifunctional protein FolD"
FT                   /id="PRO_1000185598"
FT   BINDING         161..163
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01576"
FT   BINDING         186
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01576"
FT   BINDING         227
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01576"
SQ   SEQUENCE   281 AA;  30888 MW;  A0ED70188978B4F7 CRC64;
     MSNILDGREL AKEIKERIKK ETEILEKKPR IDFLYFEDDK STEVYFTRAK KQAESVGMIG
     SLHNLPVNTT EKDFLTLIEY LNEESETSGI MIQMPLPKHI SKKKVYETIS IEKDADAISH
     VNLGRIFIGD SNLAPCTAKS AMALIEKSGI NIEGANAVVI GRSEIVGKPL AHLLLQKSAT
     VTIAHSKTKN LKELCKNADI LCVSIGKAEF ITGEYIKEGA VVIDVGINVL EDGSLKGDVN
     FEEASKLASY ITPVPNGVGS VTVSMLLDNV LYLHKNIINK K