Details of Drug-Metabolizing Enzyme (DME)

General Information of DME (ID: DME1239)
DME Name Folylpolyglutamate synthetase (fpgS), Lactobacillus casei
Synonyms Bacterial folylpoly-gamma-glutamate synthetase; Bacterial tetrahydrofolylpolyglutamate synthase; Folylpolyglutamate synthase; Bacterial FPGS; fpgS
Gene Name fpgS
UniProt ID
FPGS_LACCA
EC Number    EC: 6.3.2.17     (Click to Show/Hide the Complete EC Tree)
Ligase
Carbon-nitrogen ligase
Peptide synthase
EC: 6.3.2.17
Lineage    Species: Lactobacillus casei     (Click to Show/Hide the Complete Species Lineage)
Kingdom: Bacteria
Phylum: Firmicutes
Class: Bacilli
Order: Lactobacillales
Family: Lactobacillaceae
Genus: Lactobacillus
Species: Lactobacillus casei
Interactome
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       Interactions between Xenobiotics and DME (XEOTIC)                      
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       Interactions between Host Protein and DME (HOSPPI)                     
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      Click to Show/Hide the Molecular/Functional Data (Sequence/Structure/Pathway/Function) of This DME
Tissue Distribution Primarily distributed in human gut.
Sequence
MNYTETVAYIHSFPRLAKTGDHRRILTLLHALGNPQQQGRYIHVTGTNGKGSAANAIAHV
LEASGLTVGLYTSPFIMRFNERIMIDHEPIPDAALVNAVAFVRAALERLQQQQADFNVTE
FEFITALGYWYFRQRQVDVAVIEVGIGGDTDSTNVITPVVSVLTEVALDHQKLLGHTITA
IAKHKAGIIKRGIPVVTGNLVPDAAAVVAAKVATTGSQWLRFDRDFSVPKAKLHGWGQRF
TYEDQDGRISDLEVPLVGDYQQRNMAIAIQTAKVYAKQTEWPLTPQNIRQGLAASHWPAR
LEKISDTPLIVIDGAHNPDGINGLITALKQLFSQPITVIAGILADKDYAAMADRLTAAFS
TVYLVPVPGTPRALPEAGYEALHEGRLKDSWQEALAASLNDVPDQPIVITGSLYLASAVR
QTLLGGKS
Structure
1FGS ; 1JBV ; 1JBW ; 2GC5 ; 2GC6 ; 2GCA ; 2GCB
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.
Full List of Drug(s) Metabolized by This DME
      Drugs Approved by FDA Click to Show/Hide the Full List of Drugs:          2 Drugs
L-glutamine
 Drug Info Approved Sickle-cell anaemia ICD11: 3A51 [1]
Folic acid
 Drug Info Approved Vitamin deficiency ICD11: 5B55 [1]
Full List of Metabolic Reactions (MR) Catalyzed by This DME
MR ID Reactant Product MR Type Source Drug REF
MR005326 DACTHF Unclear Unclear - Unclear DACTHF [2]
MR001538 L-glutamine Dihydropteroate Unclear - Unclear L-glutamine [1], [3], [4]
References
1 Mutagenesis of folylpolyglutamate synthetase indicates that dihydropteroate and tetrahydrofolate bind to the same site. Biochemistry. 2008 Feb 26;47(8):2388-96.
2 Role of folylpolyglutamate synthetase in the metabolism and cytotoxicity of 5-deazaacyclotetrahydrofolate, an anti-purine drug. J Biol Chem. 1994 Apr 1;269(13):9714-20.
3 Exploring the contributions of two glutamate decarboxylase isozymes in Lactobacillus brevis to acid resistance and gamma-aminobutyric acid production. Microb Cell Fact. 2018 Nov 19;17(1):180.
4 GABA production and structure of gadB/gadC genes in Lactobacillus and Bifidobacterium strains from human microbiota. Anaerobe. 2016 Dec;42:197-204.

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