Details of Host Protein-DME Interaction (HOSPPI)

General Information of Drug-Metabolizing Enzyme (DME ID: DME1327)
DME Name	Nitroreductase (NTR), Enterococcus casseliflavus	DME Info
UniProt ID	A0A377KR04_ENTCA
EC Number	EC: 1.5.1.39 (Click to Show/Hide the Complete EC Tree) Oxidoreductase CH-NH donor oxidoreductase NAD/NADP acceptor oxidoreductase EC: 1.5.1.39
Lineage	Species: Enterococcus casseliflavus (Click to Show/Hide the Complete Species Lineage) Kingdom: Bacteria Phylum: Firmicutes Class: Bacilli Order: Lactobacillales Family: Enterococcaceae Genus: Enterococcus Species: Enterococcus casseliflavus
Interactome

Disease Specific Interactions between Host Protein and DME (HOSPPI)
Drug co-metabolism
Cometabolized drug: Metronidazole		Click to Show/Hide the Full List of HOSPPI: 6 HOSPPI
Cytochrome P450 2A6 (CYP2A6)		Click to Show/Hide the Cometabolization Info
DME ID	DME0005 DME Info
Uniprot ID	CP2A6_HUMAN
Interaction Name	CYP2A6-NTR interaction		[1], [2]
Description	The interaction, between human Cytochrome P450 2A6 and Nitroreductase from Enterococcus casseliflavus which collectively metabolize the drug Metronidazole, is reported to affect the efficacy, safety or bioavailability of this drug via interfering with it metabolism.
Cytochrome P450 2C9 (CYP2C9)		Click to Show/Hide the Cometabolization Info
DME ID	DME0019 DME Info
Uniprot ID	CP2C9_HUMAN
Interaction Name	CYP2C9-NTR interaction		[1], [3]
Description	The interaction, between human Cytochrome P450 2C9 and Nitroreductase from Enterococcus casseliflavus which collectively metabolize the drug Metronidazole, is reported to affect the efficacy, safety or bioavailability of this drug via interfering with it metabolism.
Cytochrome P450 3A4 (CYP3A4)		Click to Show/Hide the Cometabolization Info
DME ID	DME0001 DME Info
Uniprot ID	CP3A4_HUMAN
Interaction Name	CYP3A4-NTR interaction		[1], [5]
Description	The interaction, between human Cytochrome P450 3A4 and Nitroreductase from Enterococcus casseliflavus which collectively metabolize the drug Metronidazole, is reported to affect the efficacy, safety or bioavailability of this drug via interfering with it metabolism.
Cytochrome P450 3A5 (CYP3A5)		Click to Show/Hide the Cometabolization Info
DME ID	DME0012 DME Info
Uniprot ID	CP3A5_HUMAN
Interaction Name	CYP3A5-NTR interaction		[1], [2]
Description	The interaction, between human Cytochrome P450 3A5 and Nitroreductase from Enterococcus casseliflavus which collectively metabolize the drug Metronidazole, is reported to affect the efficacy, safety or bioavailability of this drug via interfering with it metabolism.
Cytochrome P450 3A7 (CYP3A7)		Click to Show/Hide the Cometabolization Info
DME ID	DME0015 DME Info
Uniprot ID	CP3A7_HUMAN
Interaction Name	CYP3A7-NTR interaction		[1], [2]
Description	The interaction, between human Cytochrome P450 3A7 and Nitroreductase from Enterococcus casseliflavus which collectively metabolize the drug Metronidazole, is reported to affect the efficacy, safety or bioavailability of this drug via interfering with it metabolism.
UDP-glucuronosyltransferase 1A1 (UGT1A1)		Click to Show/Hide the Cometabolization Info
DME ID	DME0004 DME Info
Uniprot ID	UD11_HUMAN
Interaction Name	UGT1A1-NTR interaction		[1], [7]
Description	The interaction, between human UDP-glucuronosyltransferase 1A1 and Nitroreductase from Enterococcus casseliflavus which collectively metabolize the drug Metronidazole, is reported to affect the efficacy, safety or bioavailability of this drug via interfering with it metabolism.
Cometabolized drug: Nitrofural		Click to Show/Hide the Full List of HOSPPI: 1 HOSPPI
Cytochrome P450 2D6 (CYP2D6)		Click to Show/Hide the Cometabolization Info
DME ID	DME0009 DME Info
Uniprot ID	CP2D6_HUMAN
Interaction Name	CYP2D6-NTR interaction		[1], [4]
Description	The interaction, between human Cytochrome P450 2D6 and Nitroreductase from Enterococcus casseliflavus which collectively metabolize the drug Nitrofural, is reported to affect the efficacy, safety or bioavailability of this drug via interfering with it metabolism.
Cometabolized drug: Nitrofurantoin		Click to Show/Hide the Full List of HOSPPI: 1 HOSPPI
NADPH-cytochrome P450 reductase (CPR)		Click to Show/Hide the Cometabolization Info
DME ID	DME0076 DME Info
Uniprot ID	NCPR_HUMAN
Interaction Name	CPR-NTR interaction		[1], [6]
Description	The interaction, between human NADPH-cytochrome P450 reductase and Nitroreductase from Enterococcus casseliflavus which collectively metabolize the drug Nitrofurantoin, is reported to affect the efficacy, safety or bioavailability of this drug via interfering with it metabolism.

References
1	Mechanism of metronidazole-resistance by isolates of nitroreductase-producing Enterococcus gallinarum and Enterococcus casseliflavus from the human intestinal tract. FEMS Microbiol Lett. 2003 Aug 29;225(2):195-200.
2	The role of human cytochrome P450 enzymes in the formation of 2-hydroxymetronidazole: CYP2A6 is the high affinity (low Km) catalyst. Drug Metab Dispos. 2013 Sep;41(9):1686-94.
3	Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
4	Nefazodone pharmacokinetics in depressed children and adolescents. J Am Acad Child Adolesc Psychiatry. 2000 Aug;39(8):1008-16.
5	Does metronidazole interact with CYP3A substrates by inhibiting their metabolism through this metabolic pathway? Or should other mechanisms be considered? Ann Pharmacother. 2007 Apr;41(4):653-8.
6	Role of cytochrome P450 reductase in nitrofurantoin-induced redox cycling and cytotoxicity. Free Radic Biol Med. 2008 Mar 15;44(6):1169-79.
7	Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.

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