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Protein

Folylpolyglutamate synthase

Gene

fpgS

Organism
Lactobacillus casei
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in the conversion of folates to polyglutamate derivatives, and likely functions in the retention of cellular folate pools. Catalyzes successive MgATP-dependent additions of glutamate to a pteroylmonoglutamate substrate, with a high preference for 5,10-methylenetetrahydrofolate (mTHF). Thus, metabolizes mTHF to the tetraglutamate derivative, but longer glutamate chain length products are not observed. Tetrahydrofolate (H4PteGlu) and 10-formyl-H4PteGlu are poorer folate substrates. In contrast to E.coli FolC, this enzyme does not display dihydrofolate synthase activity.2 Publications

Miscellaneous

In contrast to many bacteria such as E.coli and Corynebacterium spp., L.casei cannot synthesize folate de novo, and requires exogenous folates for growth. L.casei metabolizes folate to polyglutamates of chain length up to 11, with octa- and nonaglutamates predominating.1 Publication
Kinetic studies are consistent with an ordered Ter-Ter mechanism with MgATP binding first to the enzyme, folate second, and glutamate last. The order of product dissociation from the enzyme is ADP, folate product, and Pi.1 Publication

Catalytic activityi

ATP + tetrahydropteroyl-(gamma-Glu)(n) + L-glutamate = ADP + phosphate + tetrahydropteroyl-(gamma-Glu)(n+1).1 Publication
ATP + 5,10-methylene-tetrahydropteroyl-(gamma-Glu)(n) + L-glutamate = ADP + phosphate + 5,10-methylene-tetrahydropteroyl-(gamma-Glu)(n+1).2 Publications
ATP + 10-formyl-tetrahydropteroyl-(gamma-Glu)(n) + L-glutamate = ADP + phosphate + 10-formyl-tetrahydropteroyl-(gamma-Glu)(n+1).1 Publication

Cofactori

Mg2+1 PublicationNote: Binds 2 Mg2+ ions per subunit.1 Publication

Enzyme regulationi

Competitively inhibited by adenosine 5'-(3-thio)triphosphate and beta,gamma-methylene-ATP.1 Publication

Kineticsi

  1. KM=2.3 µM for (6R)-5,10-methylenetetrahydropteroyldiglutamate1 Publication
  2. KM=5.6 mM for ATP1 Publication
  3. KM=423 µM for glutamate1 Publication
  4. KM=32 µM for (6RS)-5,10-methylenetetrahydrofolate1 Publication
  5. KM=3.4 mM for ATP1 Publication
  6. KM=470 µM for glutamate1 Publication
  7. KM=27 µM for (6RS)-5,10-methylenetetrahydropteroyldiglutamate1 Publication
  1. Vmax=67.5 µmol/h/mg enzyme with (6R)-5,10-methylenetetrahydropteroyldiglutamate as substrate1 Publication
  2. Vmax=19 µmol/h/mg enzyme with (6RS)-5,10-methylenetetrahydrofolate as substrate1 Publication
  3. Vmax=14 µmol/h/mg enzyme with (6RS)-5,10-methylenetetrahydropteroyldiglutamate as substrate1 Publication

pH dependencei

Optimum pH is about 10.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi73Magnesium 1; via carbonyl oxygenCombined sources1 Publication1
Binding sitei75Folate substrate; via amide nitrogen and carbonyl oxygenCombined sources1 Publication1
Binding sitei82Folate substrateCombined sources1 Publication1
Metal bindingi143Magnesium 1Combined sources1 Publication1
Metal bindingi170Magnesium 2; via tele nitrogenCombined sources1 Publication1
Binding sitei264ATPCombined sources1 Publication1
Binding sitei300ATPCombined sources1 Publication1
Binding sitei417Folate substrateCombined sources1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi49 – 52ATPCombined sources1 Publication4
Nucleotide bindingi313 – 316ATPCombined sources1 Publication4

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionLigase
Biological processOne-carbon metabolism
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi6.3.2.17. 2854.
SABIO-RKiP15925.

Names & Taxonomyi

Protein namesi
Recommended name:
Folylpolyglutamate synthaseCurated (EC:6.3.2.171 Publication)
Short name:
FPGS1 Publication
Alternative name(s):
Folylpoly-gamma-glutamate synthetase1 Publication
Tetrahydrofolylpolyglutamate synthase
Gene namesi
Name:fpgSImported
OrganismiLactobacillus casei
Taxonomic identifieri1582 [NCBI]
Taxonomic lineageiBacteriaFirmicutesBacilliLactobacillalesLactobacillaceaeLactobacillus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi151D → A: 220-fold decrease in catalytic efficiency with mTHF as substrate, but only 4-fold decrease in catalytic efficiency with 5,10-methylenetetrahydropteroyldiglutamate as substrate. 1 Publication1
Mutagenesisi316H → A: Loss of activity. 1 Publication1
Mutagenesisi412S → A: Loss of activity. 1 Publication1

Chemistry databases

DrugBankiDB03801. Lysine Nz-Carboxylic Acid.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001683051 – 428Folylpolyglutamate synthaseAdd BLAST428

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei185N6-carboxylysineCombined sources1 Publication1

Interactioni

Subunit structurei

Monomer.1 Publication

Structurei

Secondary structure

1428
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi3 – 10Combined sources8
Helixi23 – 31Combined sources9
Helixi35 – 37Combined sources3
Beta strandi41 – 45Combined sources5
Beta strandi47 – 49Combined sources3
Helixi50 – 63Combined sources14
Beta strandi68 – 71Combined sources4
Beta strandi76 – 78Combined sources3
Helixi79 – 82Combined sources4
Beta strandi83 – 85Combined sources3
Helixi92 – 112Combined sources21
Helixi120 – 134Combined sources15
Beta strandi138 – 143Combined sources6
Beta strandi145 – 148Combined sources4
Beta strandi159 – 163Combined sources5
Helixi168 – 170Combined sources3
Helixi171 – 174Combined sources4
Helixi178 – 185Combined sources8
Helixi186 – 188Combined sources3
Beta strandi195 – 197Combined sources3
Helixi202 – 215Combined sources14
Beta strandi219 – 221Combined sources3
Turni222 – 224Combined sources3
Beta strandi225 – 233Combined sources9
Beta strandi235 – 244Combined sources10
Beta strandi247 – 255Combined sources9
Helixi260 – 278Combined sources19
Helixi285 – 293Combined sources9
Beta strandi300 – 305Combined sources6
Turni306 – 309Combined sources4
Beta strandi310 – 313Combined sources4
Helixi318 – 331Combined sources14
Beta strandi337 – 341Combined sources5
Beta strandi343 – 345Combined sources3
Helixi348 – 358Combined sources11
Beta strandi360 – 364Combined sources5
Helixi391 – 401Combined sources11
Beta strandi407 – 412Combined sources6
Helixi413 – 423Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1FGSX-ray2.40A1-428[»]
1JBVX-ray1.95A1-428[»]
1JBWX-ray1.85A1-428[»]
2GC5X-ray1.85A1-428[»]
2GC6X-ray1.90A1-428[»]
2GCAX-ray2.40A1-428[»]
2GCBX-ray2.30A1-428[»]
ProteinModelPortaliP15925.
SMRiP15925.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP15925.

Family & Domainsi

Sequence similaritiesi

Belongs to the folylpolyglutamate synthase family.Curated

Family and domain databases

Gene3Di3.40.1190.10. 1 hit.
3.90.190.20. 1 hit.
InterProiView protein in InterPro
IPR001645. Folylpolyglutamate_synth.
IPR018109. Folylpolyglutamate_synth_CS.
IPR004101. Mur_ligase_C.
IPR013221. Mur_ligase_cen.
PANTHERiPTHR11136. PTHR11136. 1 hit.
PfamiView protein in Pfam
PF02875. Mur_ligase_C. 1 hit.
PF08245. Mur_ligase_M. 1 hit.
PIRSFiPIRSF001563. Folylpolyglu_synth. 1 hit.
SUPFAMiSSF53244. SSF53244. 1 hit.
SSF53623. SSF53623. 1 hit.
TIGRFAMsiTIGR01499. folC. 1 hit.
PROSITEiView protein in PROSITE
PS01011. FOLYLPOLYGLU_SYNT_1. 1 hit.
PS01012. FOLYLPOLYGLU_SYNT_2. 1 hit.

Sequencei

Sequence statusi: Complete.

P15925-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNYTETVAYI HSFPRLAKTG DHRRILTLLH ALGNPQQQGR YIHVTGTNGK
60 70 80 90 100
GSAANAIAHV LEASGLTVGL YTSPFIMRFN ERIMIDHEPI PDAALVNAVA
110 120 130 140 150
FVRAALERLQ QQQADFNVTE FEFITALGYW YFRQRQVDVA VIEVGIGGDT
160 170 180 190 200
DSTNVITPVV SVLTEVALDH QKLLGHTITA IAKHKAGIIK RGIPVVTGNL
210 220 230 240 250
VPDAAAVVAA KVATTGSQWL RFDRDFSVPK AKLHGWGQRF TYEDQDGRIS
260 270 280 290 300
DLEVPLVGDY QQRNMAIAIQ TAKVYAKQTE WPLTPQNIRQ GLAASHWPAR
310 320 330 340 350
LEKISDTPLI VIDGAHNPDG INGLITALKQ LFSQPITVIA GILADKDYAA
360 370 380 390 400
MADRLTAAFS TVYLVPVPGT PRALPEAGYE ALHEGRLKDS WQEALAASLN
410 420
DVPDQPIVIT GSLYLASAVR QTLLGGKS
Length:428
Mass (Da):46,589
Last modified:April 1, 1990 - v1
Checksum:iE4B0B9ED62140181
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J05221 Genomic DNA. Translation: AAA88210.1.
PIRiA35534.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J05221 Genomic DNA. Translation: AAA88210.1.
PIRiA35534.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1FGSX-ray2.40A1-428[»]
1JBVX-ray1.95A1-428[»]
1JBWX-ray1.85A1-428[»]
2GC5X-ray1.85A1-428[»]
2GC6X-ray1.90A1-428[»]
2GCAX-ray2.40A1-428[»]
2GCBX-ray2.30A1-428[»]
ProteinModelPortaliP15925.
SMRiP15925.
ModBaseiSearch...
MobiDBiSearch...

Chemistry databases

DrugBankiDB03801. Lysine Nz-Carboxylic Acid.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Enzyme and pathway databases

BRENDAi6.3.2.17. 2854.
SABIO-RKiP15925.

Miscellaneous databases

EvolutionaryTraceiP15925.

Family and domain databases

Gene3Di3.40.1190.10. 1 hit.
3.90.190.20. 1 hit.
InterProiView protein in InterPro
IPR001645. Folylpolyglutamate_synth.
IPR018109. Folylpolyglutamate_synth_CS.
IPR004101. Mur_ligase_C.
IPR013221. Mur_ligase_cen.
PANTHERiPTHR11136. PTHR11136. 1 hit.
PfamiView protein in Pfam
PF02875. Mur_ligase_C. 1 hit.
PF08245. Mur_ligase_M. 1 hit.
PIRSFiPIRSF001563. Folylpolyglu_synth. 1 hit.
SUPFAMiSSF53244. SSF53244. 1 hit.
SSF53623. SSF53623. 1 hit.
TIGRFAMsiTIGR01499. folC. 1 hit.
PROSITEiView protein in PROSITE
PS01011. FOLYLPOLYGLU_SYNT_1. 1 hit.
PS01012. FOLYLPOLYGLU_SYNT_2. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiFPGS_LACCA
AccessioniPrimary (citable) accession number: P15925
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: April 12, 2017
This is version 105 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.