FOLC_HAEIN
ID FOLC_HAEIN Reviewed; 437 AA.
AC P43775;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 128.
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=HI_1261;
OS Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Pasteurellales;
OC Pasteurellaceae; Haemophilus.
OX NCBI_TaxID=71421;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 51907 / DSM 11121 / KW20 / Rd;
RX PubMed=7542800; DOI=10.1126/science.7542800;
RA Fleischmann R.D., Adams M.D., White O., Clayton R.A., Kirkness E.F.,
RA Kerlavage A.R., Bult C.J., Tomb J.-F., Dougherty B.A., Merrick J.M.,
RA McKenney K., Sutton G.G., FitzHugh W., Fields C.A., Gocayne J.D.,
RA Scott J.D., Shirley R., Liu L.-I., Glodek A., Kelley J.M., Weidman J.F.,
RA Phillips C.A., Spriggs T., Hedblom E., Cotton M.D., Utterback T.R.,
RA Hanna M.C., Nguyen D.T., Saudek D.M., Brandon R.C., Fine L.D.,
RA Fritchman J.L., Fuhrmann J.L., Geoghagen N.S.M., Gnehm C.L., McDonald L.A.,
RA Small K.V., Fraser C.M., Smith H.O., Venter J.C.;
RT "Whole-genome random sequencing and assembly of Haemophilus influenzae
RT Rd.";
RL Science 269:496-512(1995).
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}.
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DR EMBL; L42023; AAC22914.1; -; Genomic_DNA.
DR PIR; C64113; C64113.
DR RefSeq; NP_439416.1; NC_000907.1.
DR AlphaFoldDB; P43775; -.
DR SMR; P43775; -.
DR STRING; 71421.HI_1261; -.
DR EnsemblBacteria; AAC22914; AAC22914; HI_1261.
DR KEGG; hin:HI_1261; -.
DR PATRIC; fig|71421.8.peg.1313; -.
DR eggNOG; COG0285; Bacteria.
DR HOGENOM; CLU_015869_1_0_6; -.
DR OMA; YFEMGTL; -.
DR PhylomeDB; P43775; -.
DR BioCyc; HINF71421:G1GJ1-1289-MON; -.
DR UniPathway; UPA00077; UER00157.
DR UniPathway; UPA00850; -.
DR Proteomes; UP000000579; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008841; F:dihydrofolate synthase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004326; F:tetrahydrofolylpolyglutamate synthase activity; IBA:GO_Central.
DR GO; GO:0046656; P:folic acid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0009396; P:folic acid-containing compound biosynthetic process; IBA:GO_Central.
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 InterPro; IPR013221; Mur_ligase_cen.
DR PANTHER; PTHR11136; PTHR11136; 1.
DR Pfam; PF08245; Mur_ligase_M; 1.
DR PIRSF; PIRSF001563; Folylpolyglu_synth; 1.
DR SUPFAM; SSF53244; SSF53244; 1.
DR SUPFAM; SSF53623; SSF53623; 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..437
FT /note="Dihydrofolate synthase/folylpolyglutamate synthase"
FT /id="PRO_0000168304"
FT BINDING 28..30
FT /ligand="7,8-dihydropteroate"
FT /ligand_id="ChEBI:CHEBI:17839"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 58..61
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 82
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 120..123
FT /ligand="7,8-dihydropteroate"
FT /ligand_id="ChEBI:CHEBI:17839"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 144
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 151..153
FT /ligand="7,8-dihydropteroate"
FT /ligand_id="ChEBI:CHEBI:17839"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 171
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 255
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 287
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 316
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P08192"
SQ SEQUENCE 437 AA; 48826 MW; 04A493395E76CD43 CRC64;
MNNMQLKATS PLAEWLSYLE KSHFKPIDLG LDRIKSVAEK LDLLHPVPYV ITVGGTNGKG
TTCRLLETIL LNHGLRVGVY SSPHLLRYNE RVRIQNQDLP DEAHTASFAF IDENKTESLT
YFEFSTLSAL HLFKQAKLDV VILEVGLGGR LDATNIVDSH LAVITSIDID HTDFLGDTRE
AIAFEKAGIF RENCPVVIGE PNVPQTMLDQ AEKLHCQVAR RDVDWLFEQN AENWQWQNKK
VRLENLPFCQ IPLANAATVL AAVQYLPFDI SEQTLRKSLQ EVELVGRFQA IKTDKREKLA
DYLGVPVETL PTIIVDVGHN PHAAKYLSEK LTALKRSIEG KMIAVCGMLK DKDANGVFEH
LTPIIDEWHC VTLGGYRGQS GDELVEKLKS HFPNIQATSD NSVMDGVCTA LKSAVKNDVV
LVFGSFHTVA EFWAVVE
