Details of Drug-Metabolizing Enzyme (DME)

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

DME Name	Dihydrofolate reductase (folA)
Synonyms	DHF reductase; 5,6,7,8-tetrahydrofolate: NADP+ oxidoreductase; Bifunctional TS-DHFR; BmDHFR; Bacterial DFR-TS; Bacterial DHFR; TC_0902; folA
Gene Name	folA
UniProt ID	DYR_ECOLI
INTEDE ID	DME1049
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Gene ID	944790
EC Number	EC: 1.5.1.3 Oxidoreductase CH-NH donor oxidoreductase NAD/NADP acceptor oxidoreductase EC: 1.5.1.3
Lineage	Species: Escherichia coli Kingdom: Bacteria Phylum: Proteobacteria Class: Gammaproteobacteria Order: Enterobacterales Family: Enterobacteriaceae Genus: Escherichia Species: Escherichia coli Subspecies: Escherichia coli K-12
Tissue Distribution	Primarily distributed in human gut.
Sequence	MISLIAALAVDRVIGMENAMPWNLPADLAWFKRNTLNKPVIMGRHTWESIGRPLPGRKNI ILSSQPGTDDRVTWVKSVDEAIAACGDVPEIMVIGGGRVYEQFLPKAQKLYLTHIDAEVE GDTHFPDYEPDDWESVFSEFHDADAQNSHSYCFEILERR
Function	This enzyme is key enzyme in folate metabolism and can catalyze an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. And it also slowly reduces folate to 5,6,7,8-tetrahydrofolate.
KEGG Pathway	Folate biosynthesis (ecj00790 ) Metabolic pathways (ecj01100 ) One carbon pool by folate (ecj00670 )

Molecular Interaction Atlas (MIA) of This DME

Molecular Interaction Atlas (MIA)

Jump to Detail Molecular Interaction Atlas 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	[5], [6]
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The Drug Therapeutic Target (DTT) Role of This DME

DME DTT Name

Bacterial Dihydrofolate reductase (Bact DHFR) DTT Info

DME DTT Type

Clinical trial

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Iclaprim	DM7YNV9	Bacterial infection	1A00-1C4Z	Phase 3	[1]
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3 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AR-709	DMUI81C	Bacterial infection	1A00-1C4Z	Terminated	[2]
DIAVERIDINE	DMB74CM	Bacterial infection	1A00-1C4Z	Terminated	[3]
Epiroprim	DM6IY4M	Bacterial infection	1A00-1C4Z	Terminated	[4]
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References

1	Iclaprim: a novel dihydrofolate reductase inhibitor for skin and soft tissue infections.Future Microbiol.2009 Mar;4(2):131-44.
2	Activity of the Diaminopyrimidine AR-709 against Recently Collected Multidrug-Resistant Isolates of Invasive Streptococcus pneumoniae from North America
3	Acute and sub-chronic toxicity study of diaveridine in Wistar rats.Regul Toxicol Pharmacol.2015 Oct;73(1):232-40.
4	In vitro activity of epiroprim, a dihydrofolate reductase inhibitor, singly and in combination with brodimoprim and dapsone, against Mycobacterium ... Int J Antimicrob Agents. 1999 Aug;12(4):319-23.
5	Measurement of the uptake of radioactive para-aminobenzoic acid monitors folate biosynthesis in Escherichia coli K-12. Anal Biochem. 1994 Feb 1;216(2):427-30.
6	The influence of CsgD on the expression of genes of folate metabolism and hmp in Escherichia coli K-12. Arch Microbiol. 2013 Aug;195(8):559-69.