ID   FOLD_CLOBJ              Reviewed;         282 AA.
AC   C1FKP7;
DT   28-JUL-2009, integrated into UniProtKB/Swiss-Prot.
DT   26-MAY-2009, sequence version 1.
DT   03-AUG-2022, entry version 68.
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=CLM_1323;
OS   Clostridium botulinum (strain Kyoto / Type A2).
OC   Bacteria; Firmicutes; Clostridia; Eubacteriales; Clostridiaceae;
OC   Clostridium.
OX   NCBI_TaxID=536232;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Kyoto / Type A2;
RA   Shrivastava S., Brinkac L.M., Brown J.L., Bruce D., Detter C.C.,
RA   Johnson E.A., Munk C.A., Smith L.A., Smith T.J., Sutton G., Brettin T.S.;
RT   "Genome sequence of Clostridium botulinum A2 Kyoto.";
RL   Submitted (OCT-2008) to the EMBL/GenBank/DDBJ databases.
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; CP001581; ACO85580.1; -; Genomic_DNA.
DR   RefSeq; WP_012704834.1; NC_012563.1.
DR   AlphaFoldDB; C1FKP7; -.
DR   SMR; C1FKP7; -.
DR   STRING; 536232.CLM_1323; -.
DR   EnsemblBacteria; ACO85580; ACO85580; CLM_1323.
DR   KEGG; cby:CLM_1323; -.
DR   eggNOG; COG0190; Bacteria.
DR   HOGENOM; CLU_034045_2_1_9; -.
DR   OMA; KACSKEI; -.
DR   UniPathway; UPA00193; -.
DR   Proteomes; UP000001374; 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..282
FT                   /note="Bifunctional protein FolD"
FT                   /id="PRO_1000185604"
FT   BINDING         165..167
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01576"
FT   BINDING         190
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;  31688 MW;  C32017263338C1C0 CRC64;
     MTKILYGNEV ALKIKEDLNL RIDKLKEKNI IPKLAILRMG NKPDDIAYER SIIKSCEKLN
     IETKVEELNE DILEEDFLKL MESLNNEKEI HGILVFRPYP KHLNENTINS SIALNKDVDC
     MHPLNLERIF EGDLNQFVPC TPEAVIEILK YYDIDLKGKN IVIINRSMVV GKPLSMMVLS
     NNATVTICHS KTIDLPSITK KADIVVTAIG KAKLIKEEYF NEDSIVMDVS INVDENGKLC
     GDVDFENVKE KVGAITPVPK GVGSVTTTLL LKHIVDAAER NS