ID FOLC_BUCAI Reviewed; 411 AA. AC P57265; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2000, sequence version 1. DT 14-DEC-2022, entry version 114. DE RecName: Full=Dihydrofolate synthase/folylpolyglutamate synthase; DE Short=DHFS / FPGS; DE EC=6.3.2.12; DE EC=6.3.2.17; DE AltName: Full=Folylpoly-gamma-glutamate synthetase-dihydrofolate synthetase; DE AltName: Full=Folylpolyglutamate synthetase; DE AltName: Full=Tetrahydrofolylpolyglutamate synthase; GN Name=folC; OrderedLocusNames=BU167; OS Buchnera aphidicola subsp. Acyrthosiphon pisum (strain APS) (Acyrthosiphon OS pisum symbiotic bacterium). OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales; OC Erwiniaceae; Buchnera. OX NCBI_TaxID=107806; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=APS; RX PubMed=10993077; DOI=10.1038/35024074; RA Shigenobu S., Watanabe H., Hattori M., Sakaki Y., Ishikawa H.; RT "Genome sequence of the endocellular bacterial symbiont of aphids Buchnera RT sp. APS."; RL Nature 407:81-86(2000). CC -!- FUNCTION: Functions in two distinct reactions of the de novo folate CC biosynthetic pathway. Catalyzes the addition of a glutamate residue to CC dihydropteroate (7,8-dihydropteroate or H2Pte) to form dihydrofolate CC (7,8-dihydrofolate monoglutamate or H2Pte-Glu). Also catalyzes CC successive additions of L-glutamate to tetrahydrofolate or 10- CC formyltetrahydrofolate or 5,10-methylenetetrahydrofolate, leading to CC folylpolyglutamate derivatives. {ECO:0000250|UniProtKB:P08192}. CC -!- CATALYTIC ACTIVITY: CC Reaction=7,8-dihydropteroate + ATP + L-glutamate = 7,8-dihydrofolate + CC ADP + H(+) + phosphate; Xref=Rhea:RHEA:23584, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:17839, ChEBI:CHEBI:29985, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57451, ChEBI:CHEBI:456216; CC EC=6.3.2.12; Evidence={ECO:0000250|UniProtKB:P08192}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(6S)-5,6,7,8-tetrahydrofolyl-(gamma-L-Glu)(n) + ATP + L- CC glutamate = (6S)-5,6,7,8-tetrahydrofolyl-(gamma-L-Glu)(n+1) + ADP + CC H(+) + phosphate; Xref=Rhea:RHEA:10580, Rhea:RHEA-COMP:14738, CC Rhea:RHEA-COMP:14740, ChEBI:CHEBI:15378, ChEBI:CHEBI:29985, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:141005, CC ChEBI:CHEBI:456216; EC=6.3.2.17; CC Evidence={ECO:0000250|UniProtKB:P08192}; CC -!- CATALYTIC ACTIVITY: CC Reaction=10-formyltetrahydrofolyl-(gamma-L-Glu)(n) + ATP + L-glutamate CC = 10-formyltetrahydrofolyl-(gamma-L-Glu)(n+1) + ADP + H(+) + CC phosphate; Xref=Rhea:RHEA:51904, Rhea:RHEA-COMP:13088, Rhea:RHEA- CC COMP:14300, ChEBI:CHEBI:15378, ChEBI:CHEBI:29985, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:134413, ChEBI:CHEBI:456216; CC EC=6.3.2.17; Evidence={ECO:0000250|UniProtKB:P08192}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(6R)-5,10-methylenetetrahydrofolyl-(gamma-L-Glu)(n) + ATP + L- CC glutamate = (6R)-5,10-methylenetetrahydrofolyl-(gamma-L-Glu)(n+1) + CC ADP + H(+) + phosphate; Xref=Rhea:RHEA:51912, Rhea:RHEA-COMP:13257, CC Rhea:RHEA-COMP:13258, ChEBI:CHEBI:15378, ChEBI:CHEBI:29985, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:136572, CC ChEBI:CHEBI:456216; EC=6.3.2.17; CC Evidence={ECO:0000250|UniProtKB:P08192}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:P08192}; CC Note=Binds 2 Mg(2+) ions per subunit. {ECO:0000250|UniProtKB:P08192}; CC -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 7,8- CC dihydrofolate from 2-amino-4-hydroxy-6-hydroxymethyl-7,8- CC dihydropteridine diphosphate and 4-aminobenzoate: step 2/2. CC {ECO:0000250|UniProtKB:P08192}. CC -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolylpolyglutamate CC biosynthesis. {ECO:0000250|UniProtKB:P08192}. CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P08192}. CC -!- SIMILARITY: Belongs to the folylpolyglutamate synthase family. CC {ECO:0000305}. 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; BA000003; BAB12885.1; -; Genomic_DNA. DR RefSeq; NP_239999.1; NC_002528.1. DR RefSeq; WP_010895983.1; NC_002528.1. DR AlphaFoldDB; P57265; -. DR SMR; P57265; -. DR STRING; 107806.10038850; -. DR EnsemblBacteria; BAB12885; BAB12885; BAB12885. DR KEGG; buc:BU167; -. DR PATRIC; fig|107806.10.peg.177; -. DR eggNOG; COG0285; Bacteria. DR HOGENOM; CLU_015869_1_0_6; -. DR OMA; YFEMGTL; -. DR UniPathway; UPA00077; UER00157. DR UniPathway; UPA00850; -. DR Proteomes; UP000001806; Chromosome. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0008841; F:dihydrofolate synthase activity; IEA:UniProtKB-EC. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004326; F:tetrahydrofolylpolyglutamate synthase activity; IEA:UniProtKB-EC. DR GO; GO:0046656; P:folic acid biosynthetic process; IEA:UniProtKB-KW. DR GO; GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-KW. DR GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IEA:UniProtKB-UniPathway. DR Gene3D; 3.40.1190.10; -; 1. DR Gene3D; 3.90.190.20; -; 1. DR InterPro; IPR001645; Folylpolyglutamate_synth. DR InterPro; IPR018109; Folylpolyglutamate_synth_CS. DR InterPro; IPR036565; Mur-like_cat_sf. DR InterPro; IPR036615; Mur_ligase_C_dom_sf. DR PANTHER; PTHR11136; FOLYLPOLYGLUTAMATE SYNTHASE-RELATED; 1. DR PIRSF; PIRSF001563; Folylpolyglu_synth; 1. DR SUPFAM; SSF53623; MurD-like peptide ligases, catalytic domain; 1. DR SUPFAM; SSF53244; MurD-like peptide ligases, peptide-binding domain; 1. DR TIGRFAMs; TIGR01499; folC; 1. DR PROSITE; PS01011; FOLYLPOLYGLU_SYNT_1; 1. DR PROSITE; PS01012; FOLYLPOLYGLU_SYNT_2; 1. PE 3: Inferred from homology; KW ATP-binding; Folate biosynthesis; Ligase; Magnesium; Metal-binding; KW Nucleotide-binding; One-carbon metabolism; Reference proteome. FT CHAIN 1..411 FT /note="Dihydrofolate synthase/folylpolyglutamate synthase" FT /id="PRO_0000168300" FT BINDING 53..56 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P08192" FT BINDING 77 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P08192" FT BINDING 116..119 FT /ligand="7,8-dihydropteroate" FT /ligand_id="ChEBI:CHEBI:17839" FT /evidence="ECO:0000250|UniProtKB:P08192" FT BINDING 147..149 FT /ligand="7,8-dihydropteroate" FT /ligand_id="ChEBI:CHEBI:17839" FT /evidence="ECO:0000250|UniProtKB:P08192" FT BINDING 167 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P08192" FT BINDING 283 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P08192" FT BINDING 296 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P08192" SQ SEQUENCE 411 AA; 46970 MW; 5DDC2DC66539935A CRC64; MINKNYSLSL WLKYLEQLDK KRIYNLTELK FLAKKLGLLK SESFIFTVAG TNGKGTTCAV LERLLLDSGY QVGLYTSPHL INFVERVRIN GFVLHEEEHI DSFQNVELVR NGVLLTYFEF ITLAALILFK RYSLDCIILK VGLGGRLDAT NIIDSDISII TNIGIDHTSI LGRDRISIAR EKCGVFRKNK ISVIGETDIP CSMYQIAKEK KTILKKIDID WSWEKKRNYW NFFHSTIQLY NLPETQVPLS SAATALSTLY YSRFKIKEKI IRKSISNVQL PGRFQVISTF PYIIVDVAHN PNAAFYLSQK IDEINITGKI YAVVGILKDK DILGIIDPLA NKIHHWFTAP LKTIRTATKH ELKKFFPIHN TSILKSIEIA YKKALILVKK EDAIIIFGSF LTVSEFLSLK I //