ID FOLC_BUCAP Reviewed; 418 AA. AC Q8K9X3; DT 08-NOV-2002, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2002, sequence version 1. DT 27-MAR-2024, entry version 118. 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=BUsg_161; OS Buchnera aphidicola subsp. Schizaphis graminum (strain Sg). OC Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales; OC Erwiniaceae; Buchnera. OX NCBI_TaxID=198804; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Sg; RX PubMed=12089438; DOI=10.1126/science.1071278; RA Tamas I., Klasson L., Canbaeck B., Naeslund A.K., Eriksson A.-S., RA Wernegreen J.J., Sandstroem J.P., Moran N.A., Andersson S.G.E.; RT "50 million years of genomic stasis in endosymbiotic bacteria."; RL Science 296:2376-2379(2002). 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; AE013218; AAM67729.1; -; Genomic_DNA. DR RefSeq; WP_011053696.1; NC_004061.1. DR AlphaFoldDB; Q8K9X3; -. DR SMR; Q8K9X3; -. DR STRING; 198804.BUsg_161; -. DR GeneID; 75258962; -. DR KEGG; bas:BUsg_161; -. DR eggNOG; COG0285; Bacteria. DR HOGENOM; CLU_015869_1_0_6; -. DR UniPathway; UPA00077; UER00157. DR UniPathway; UPA00850; -. DR Proteomes; UP000000416; 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; 3.90.190.20; Mur ligase, C-terminal domain; 1. DR Gene3D; 3.40.1190.10; Mur-like, catalytic domain; 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 InterPro; IPR013221; Mur_ligase_cen. DR NCBIfam; TIGR01499; folC; 1. DR PANTHER; PTHR11136:SF0; DIHYDROFOLATE SYNTHETASE-RELATED; 1. DR PANTHER; PTHR11136; FOLYLPOLYGLUTAMATE SYNTHASE-RELATED; 1. DR Pfam; PF08245; Mur_ligase_M; 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 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. FT CHAIN 1..418 FT /note="Dihydrofolate synthase/folylpolyglutamate synthase" FT /id="PRO_0000168301" 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 140 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" 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 252 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P08192" FT BINDING 284 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P08192" FT BINDING 297 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P08192" SQ SEQUENCE 418 AA; 47631 MW; 6F644AFF9144AED4 CRC64; MHKKKYTFSM WMKYLEKFDK KDRKNLFELK LIAKKLGLLN LKSFFFTVGG TNGKGTTCAM LEKLLLDSGY QVGLYTSPHL INYSERIKVN GLYLSEKDHI FSFLIIDAEK GNVSLTYFEF ITLSALFLFS QYSLDIIILE VGLGGRLDAT NIIDSDLSVI TNIGIDHTSC LGTDRISIGR EKSGIFRKGK IAVIGEKNIP ISVDEIAKEK KTILKKIDVD WFWTRTKIDS WNFIHSNIEL YNLPVSRIPL SNTAIALASL FYSGLEVNLK KLKSSISKVQ LSGRFQTVFN SPRIILDVAH NVHAALYLSE KIDEIDTEGQ IYAVFGILKD KDVAGVVQVL QKKINYWYVV NLKTNRSASI NYLKKKLSLN NALFFNNINE SWQAIKKVIT KKDIILVFGS FFTVSEFMSI KDRRLTLY //