Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DEW0GI5)

• DME Name: Folylpolyglutamate synthetase (fpgS)
• Synonyms: Bacterial folylpoly-gamma-glutamate synthetase; Bacterial tetrahydrofolylpolyglutamate synthase; Folylpolyglutamate synthase; Bacterial FPGS; fpgS
• Gene Name: fpgS
• UniProt ID: FPGS_LACCA
• INTEDE ID: DME1239
• EC Number:
  EC: 6.3.2.17
  Ligase
  Carbon-nitrogen ligase
  Peptide synthase
  EC: 6.3.2.17
• Lineage:
  Species: Lactobacillus casei
  Kingdom: Bacteria
  Phylum: Firmicutes
  Class: Bacilli
  Order: Lactobacillales
  Family: Lactobacillaceae
  Genus: Lactobacillus
  Species: Lactobacillus casei
• Tissue Distribution: Primarily distributed in human gut.
• Sequence:
  MNYTETVAYIHSFPRLAKTGDHRRILTLLHALGNPQQQGRYIHVTGTNGKGSAANAIAHV
  LEASGLTVGLYTSPFIMRFNERIMIDHEPIPDAALVNAVAFVRAALERLQQQQADFNVTE
  FEFITALGYWYFRQRQVDVAVIEVGIGGDTDSTNVITPVVSVLTEVALDHQKLLGHTITA
  IAKHKAGIIKRGIPVVTGNLVPDAAAVVAAKVATTGSQWLRFDRDFSVPKAKLHGWGQRF
  TYEDQDGRISDLEVPLVGDYQQRNMAIAIQTAKVYAKQTEWPLTPQNIRQGLAASHWPAR
  LEKISDTPLIVIDGAHNPDGINGLITALKQLFSQPITVIAGILADKDYAAMADRLTAAFS
  TVYLVPVPGTPRALPEAGYEALHEGRLKDSWQEALAASLNDVPDQPIVITGSLYLASAVR
  QTLLGGKS
• Function: This enzyme is involved in the conversion of folates to polyglutamate derivatives, and likely functions in the retention of cellular folate pools. It catalyzes successive MgATP-dependent additions of glutamate to a pteroylmonoglutamate substrate, with a high preference for 5,10-methylenetetrahydrofolate (mTHF). Thus, it metabolizes mTHF to the tetraglutamate derivative, but longer glutamate chain length products are not observed.

Molecular Interaction Atlas (MIA) of This DME

1 Approved Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[1]

References

• [1] Mutagenesis of folylpolyglutamate synthetase indicates that dihydropteroate and tetrahydrofolate bind to the same site. Biochemistry. 2008 Feb 26;47(8):2388-96.