Folyl polyglutamate synthetase

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Folyl polyglutamate synthetase
Properties of human protein
Mass / length primary structure 545 amino acids
Secondary to quaternary structure Monomer
Isoforms 2
Identifier
Gene name FPGS
External IDs
Enzyme classification
EC, category 6.3.2.17 ligase
Response type Addition of a glutamate residue
Substrate ATP + folyl- (γ-Glu) n + L -Glu
Products ADP + P i + folyl- (γ-Glu) (n + 1)
Occurrence
Homology family FPGS
Parent taxon Eukaryotes
Orthologue
human House mouse
Entrez 2356 14287
Ensemble ENSG00000136877 ENSMUSG00000009566
UniProt Q05932 P48760
Refseq (mRNA) NM_001018078 NM_010236
Refseq (protein) NP_001018088 NP_034366
Gene locus Chr 9: 127.79 - 127.81 Mb Chr 2: 32.68 - 32.7 Mb
PubMed search 2356 14287

The Folylpolyglutamat synthase ( FPGS ) is an enzyme , the ATP -dependent L - glutamate residues at reduced folic acid - derivatives ligated .

These substances can only be stored in the cell (in the cytosol and mitochondrion ) as polyglutamate , and only in this form do they take part in several important metabolic reactions as cofactors . The optimal number at which the cofactors are the most effective reaction partners is six glutamate molecules in humans. FPGS is part of almost all living things.

Folic acid antagonists are also accepted as substrates by FPGS . Resistance of cancer cells to these drugs may be partly mutations on FPGS - gene with the following enzyme deficiency have as the cause, because the substances are transported out again unchanged from the cell. Inhibitors against FPGS themselves are also used in chemotherapy.

Individual evidence

  1. UniProt Q05932
  2. reactome.org: Conversion of mitochondrial THF to THF-polyglutamate  ( page no longer available , search in web archivesInfo: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice.@1@ 2Template: dead link / reactome.org  
  3. reactome.org: Conversion of cytosolic 5-methyltetrahydrofolate (5-methylTHF) to 5-methylTHF-polyglutamate  ( page no longer available , search in web archivesInfo: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice.@1@ 2Template: dead link / reactome.org  
  4. Leclerc GJ, York TA, Hsieh-Kinser T, Barredo JC: Molecular basis for decreased folylpoly-gamma-glutamate synthetase expression in a methotrexate resistant CCRF-CEM mutant cell line . In: Leukemia Research . 31, No. 3, March 2007, pp. 293-9. doi : 10.1016 / j.leukres.2006.06.016 . PMID 16884772 .
  5. Gangjee A, Dubash NP, Zeng Y, McGuire JJ: Recent advances in the chemistry and biology of folypoly-gamma-glutamate synthetase substrates and inhibitors . In: Curr Med Chem Anticancer Agents . 2, No. 3, May 2002, pp. 331-55. PMID 12678736 .