ID A0A140D693_9GAMM Unreviewed; 297 AA. AC A0A140D693; DT 11-MAY-2016, integrated into UniProtKB/TrEMBL. DT 11-MAY-2016, sequence version 1. DT 08-NOV-2023, entry version 38. DE RecName: Full=Bifunctional protein FolD {ECO:0000256|HAMAP-Rule:MF_01576}; DE Includes: DE RecName: Full=Methylenetetrahydrofolate dehydrogenase {ECO:0000256|HAMAP-Rule:MF_01576}; DE EC=1.5.1.5 {ECO:0000256|HAMAP-Rule:MF_01576}; DE Includes: DE RecName: Full=Methenyltetrahydrofolate cyclohydrolase {ECO:0000256|HAMAP-Rule:MF_01576}; DE EC=3.5.4.9 {ECO:0000256|HAMAP-Rule:MF_01576}; GN Name=mthD {ECO:0000313|EMBL:AMK07367.1}; GN Synonyms=folD {ECO:0000256|HAMAP-Rule:MF_01576}; OS gamma proteobacterium 10BT. OC Bacteria; Pseudomonadota; Gammaproteobacteria. OX NCBI_TaxID=1778877 {ECO:0000313|EMBL:AMK07367.1}; RN [1] {ECO:0000313|EMBL:AMK07367.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=10BTContig1 {ECO:0000313|EMBL:AMK07367.1}; RX PubMed=26822785; DOI=10.1186/s12864-016-2404-0; RA Maruthamuthu M., Jimenez D.J., Stevens P., van Elsas J.D.; RT "A multi-substrate approach for functional metagenomics-based screening for RT (hemi)cellulases in two wheat straw-degrading microbial consortia unveils RT novel thermoalkaliphilic enzymes."; RL BMC Genomics 17:86-86(2016). 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:0000256|HAMAP-Rule:MF_01576}. 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:0000256|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:0000256|HAMAP- CC Rule:MF_01576}; CC -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion. CC {ECO:0000256|HAMAP-Rule:MF_01576}. CC -!- SUBUNIT: Homodimer. {ECO:0000256|HAMAP-Rule:MF_01576}. CC -!- SIMILARITY: Belongs to the tetrahydrofolate CC dehydrogenase/cyclohydrolase family. {ECO:0000256|HAMAP-Rule:MF_01576}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; KU505133; AMK07367.1; -; Genomic_DNA. DR AlphaFoldDB; A0A140D693; -. 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 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 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; PS00767; THF_DHG_CYH_2; 1. PE 3: Inferred from homology; KW Amino-acid biosynthesis {ECO:0000256|ARBA:ARBA00022605, ECO:0000256|HAMAP- KW Rule:MF_01576}; KW Histidine biosynthesis {ECO:0000256|ARBA:ARBA00023102, ECO:0000256|HAMAP- KW Rule:MF_01576}; KW Hydrolase {ECO:0000256|ARBA:ARBA00022801, ECO:0000256|HAMAP-Rule:MF_01576}; KW Methionine biosynthesis {ECO:0000256|ARBA:ARBA00023167, ECO:0000256|HAMAP- KW Rule:MF_01576}; KW Multifunctional enzyme {ECO:0000256|ARBA:ARBA00023268, ECO:0000256|HAMAP- KW Rule:MF_01576}; KW NADP {ECO:0000256|ARBA:ARBA00022857, ECO:0000256|HAMAP-Rule:MF_01576}; KW One-carbon metabolism {ECO:0000256|ARBA:ARBA00022563, ECO:0000256|HAMAP- KW Rule:MF_01576}; KW Oxidoreductase {ECO:0000256|ARBA:ARBA00023002, ECO:0000256|HAMAP- KW Rule:MF_01576}; KW Purine biosynthesis {ECO:0000256|ARBA:ARBA00022755, ECO:0000256|HAMAP- KW Rule:MF_01576}. FT DOMAIN 10..124 FT /note="Tetrahydrofolate dehydrogenase/cyclohydrolase FT catalytic" FT /evidence="ECO:0000259|Pfam:PF00763" FT DOMAIN 127..285 FT /note="Tetrahydrofolate dehydrogenase/cyclohydrolase FT NAD(P)-binding" FT /evidence="ECO:0000259|Pfam:PF02882" FT BINDING 169..171 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01576" FT BINDING 194 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01576" FT BINDING 235 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01576" SQ SEQUENCE 297 AA; 31485 MW; B41D2755AF1337B4 CRC64; MSAVPGVKLI DGKATAARVL AEVREQVLEL RQGGVQPGLA VVLVGADAAS HVYVRNKVLR AEEVGIRSLE HRLHADTTQA HLLALIDRLN RDPEVNGILV QLPLPGHIDE HRVLQAISPF KDVDGFHSEN VGGLAQGRDV LTPCTPSACM RLLRDACGEL RGKHAVVVGR SNIVGKPMAA LLLQADCTVT VVHSHSRDLP ALCRQADILV AAVGQPRLIG ADWLKPGAVV IDVGINRVDD GGHSRLVGDV DFAAALPQVA GITPVPGGVG PMTIAYLMKN TLLALDLQQQ AAHQERT //