FOLD_ECOLI
ID FOLD_ECOLI Reviewed; 288 AA.
AC P24186; P77132; Q2MBQ0;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 169.
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}; Synonyms=ads;
GN OrderedLocusNames=b0529, JW0518;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-36, FUNCTION, AND
RP SUBUNIT.
RX PubMed=1748668; DOI=10.1016/s0021-9258(18)54377-5;
RA D'Ari L., Rabinowitz J.C.;
RT "Purification, characterization, cloning, and amino acid sequence of the
RT bifunctional enzyme 5,10-methylenetetrahydrofolate dehydrogenase/5,10-
RT methenyltetrahydrofolate cyclohydrolase from Escherichia coli.";
RL J. Biol. Chem. 266:23953-23958(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RA Yonetani Y., Sanpei G., Mizobuchi K.;
RT "Cloning and nucleotide sequence analysis of a novel adenine-sensitive
RT mutation of Escherichia coli strain K-12 W3110.";
RL Submitted (JUL-1992) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RA Chung E., Allen E., Araujo R., Aparicio A.M., Davis K., Duncan M.,
RA Federspiel N., Hyman R., Kalman S., Komp C., Kurdi O., Lew H., Lin D.,
RA Namath A., Oefner P., Roberts D., Schramm S., Davis R.W.;
RT "Sequence of minutes 4-25 of Escherichia coli.";
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 [5]
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 [6]
RP X-RAY CRYSTALLOGRAPHY (2.56 ANGSTROMS), AND SUBUNIT.
RX PubMed=10386884; DOI=10.1110/ps.8.6.1342;
RA Shen B.W., Dyer D.H., Huang J.-Y., D'Ari L., Rabinowitz J., Stoddard B.L.;
RT "The crystal structure of a bacterial, bifunctional 5,10 methylene-
RT tetrahydrofolate dehydrogenase/cyclohydrolase.";
RL Protein Sci. 8:1342-1349(1999).
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. This enzyme is
CC specific for NADP. {ECO:0000255|HAMAP-Rule:MF_01576,
CC ECO:0000269|PubMed:1748668}.
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 ECO:0000269|PubMed:10386884, ECO:0000269|PubMed:1748668}.
CC -!- SIMILARITY: Belongs to the tetrahydrofolate
CC dehydrogenase/cyclohydrolase family. {ECO:0000255|HAMAP-Rule:MF_01576}.
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DR EMBL; M74789; AAA23803.1; -; Genomic_DNA.
DR EMBL; D10588; BAA01445.1; -; Genomic_DNA.
DR EMBL; U82664; AAB40282.1; -; Genomic_DNA.
DR EMBL; U00096; AAC73631.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE76306.1; -; Genomic_DNA.
DR PIR; H64784; JS0662.
DR RefSeq; NP_415062.1; NC_000913.3.
DR RefSeq; WP_000729160.1; NZ_STEB01000007.1.
DR PDB; 1B0A; X-ray; 2.56 A; A=1-288.
DR PDB; 5O22; X-ray; 2.10 A; A/B/C/D=2-288.
DR PDB; 5O28; X-ray; 1.89 A; A/B/C/D=2-288.
DR PDB; 5O2A; X-ray; 1.90 A; A/B/C/D=2-288.
DR PDBsum; 1B0A; -.
DR PDBsum; 5O22; -.
DR PDBsum; 5O28; -.
DR PDBsum; 5O2A; -.
DR AlphaFoldDB; P24186; -.
DR SMR; P24186; -.
DR BioGRID; 4262819; 297.
DR DIP; DIP-9675N; -.
DR IntAct; P24186; 4.
DR STRING; 511145.b0529; -.
DR jPOST; P24186; -.
DR PaxDb; P24186; -.
DR PRIDE; P24186; -.
DR EnsemblBacteria; AAC73631; AAC73631; b0529.
DR EnsemblBacteria; BAE76306; BAE76306; BAE76306.
DR GeneID; 945221; -.
DR KEGG; ecj:JW0518; -.
DR KEGG; eco:b0529; -.
DR PATRIC; fig|1411691.4.peg.1749; -.
DR EchoBASE; EB0324; -.
DR eggNOG; COG0190; Bacteria.
DR HOGENOM; CLU_034045_2_1_6; -.
DR InParanoid; P24186; -.
DR OMA; HIVGRPM; -.
DR PhylomeDB; P24186; -.
DR BioCyc; EcoCyc:FOLD-MON; -.
DR BioCyc; MetaCyc:FOLD-MON; -.
DR BRENDA; 1.5.1.5; 2026.
DR BRENDA; 3.5.4.9; 2026.
DR SABIO-RK; P24186; -.
DR UniPathway; UPA00193; -.
DR EvolutionaryTrace; P24186; -.
DR PRO; PR:P24186; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005829; C:cytosol; IDA:EcoCyc.
DR GO; GO:0004477; F:methenyltetrahydrofolate cyclohydrolase activity; IDA:EcoCyc.
DR GO; GO:0004488; F:methylenetetrahydrofolate dehydrogenase (NADP+) activity; IDA:EcoCyc.
DR GO; GO:0000105; P:histidine biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0009086; P:methionine biosynthetic process; IMP:EcoCyc.
DR GO; GO:0006164; P:purine nucleotide biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0035999; P:tetrahydrofolate interconversion; IBA:GO_Central.
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 1: Evidence at protein level;
KW 3D-structure; Amino-acid biosynthesis; Direct protein sequencing;
KW Histidine biosynthesis; Hydrolase; Methionine biosynthesis;
KW Multifunctional enzyme; NADP; One-carbon metabolism; Oxidoreductase;
KW Purine biosynthesis; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:1748668"
FT CHAIN 2..288
FT /note="Bifunctional protein FolD"
FT /id="PRO_0000199306"
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"
FT CONFLICT 47
FT /note="S -> L (in Ref. 3; AAB40282)"
FT /evidence="ECO:0000305"
FT CONFLICT 200
FT /note="V -> L (in Ref. 1; AAA23803)"
FT /evidence="ECO:0000305"
FT HELIX 8..21
FT /evidence="ECO:0007829|PDB:5O28"
FT HELIX 24..28
FT /evidence="ECO:0007829|PDB:5O28"
FT STRAND 35..42
FT /evidence="ECO:0007829|PDB:5O28"
FT HELIX 45..60
FT /evidence="ECO:0007829|PDB:5O28"
FT STRAND 64..70
FT /evidence="ECO:0007829|PDB:5O28"
FT HELIX 76..88
FT /evidence="ECO:0007829|PDB:5O28"
FT STRAND 94..97
FT /evidence="ECO:0007829|PDB:5O28"
FT HELIX 107..113
FT /evidence="ECO:0007829|PDB:5O28"
FT HELIX 116..118
FT /evidence="ECO:0007829|PDB:5O28"
FT HELIX 125..132
FT /evidence="ECO:0007829|PDB:5O28"
FT HELIX 141..152
FT /evidence="ECO:0007829|PDB:5O28"
FT STRAND 161..165
FT /evidence="ECO:0007829|PDB:5O28"
FT TURN 169..171
FT /evidence="ECO:0007829|PDB:5O28"
FT HELIX 172..181
FT /evidence="ECO:0007829|PDB:5O28"
FT STRAND 185..189
FT /evidence="ECO:0007829|PDB:5O28"
FT HELIX 196..201
FT /evidence="ECO:0007829|PDB:5O28"
FT STRAND 204..208
FT /evidence="ECO:0007829|PDB:5O28"
FT HELIX 218..220
FT /evidence="ECO:0007829|PDB:5O28"
FT STRAND 226..229
FT /evidence="ECO:0007829|PDB:5O28"
FT STRAND 238..241
FT /evidence="ECO:0007829|PDB:5O28"
FT HELIX 246..250
FT /evidence="ECO:0007829|PDB:5O28"
FT STRAND 254..256
FT /evidence="ECO:0007829|PDB:5O28"
FT STRAND 259..263
FT /evidence="ECO:0007829|PDB:5O28"
FT HELIX 264..282
FT /evidence="ECO:0007829|PDB:5O28"
SQ SEQUENCE 288 AA; 31044 MW; 028039D7C611085D CRC64;
MAAKIIDGKT IAQQVRSEVA QKVQARIAAG LRAPGLAVVL VGSNPASQIY VASKRKACEE
VGFVSRSYDL PETTSEAELL ELIDTLNADN TIDGILVQLP LPAGIDNVKV LERIHPDKDV
DGFHPYNVGR LCQRAPRLRP CTPRGIVTLL ERYNIDTFGL NAVVIGASNI VGRPMSMELL
LAGCTTTVTH RFTKNLRHHV ENADLLIVAV GKPGFIPGDW IKEGAIVIDV GINRLENGKV
VGDVVFEDAA KRASYITPVP GGVGPMTVAT LIENTLQACV EYHDPQDE
