Details of Host Protein-DME Interaction (HOSPPI)

General Information of Drug-Metabolizing Enzyme (DME ID: DME1048)
DME Name Oxygen-insensitive NADPH nitroreductase B (nfsB), Escherichia coli DME Info
UniProt ID
NFSB_ECOLI
EC Number    EC: 1.5.1.34     (Click to Show/Hide the Complete EC Tree)
Oxidoreductase
CH-NH donor oxidoreductase
NAD/NADP acceptor oxidoreductase
EC: 1.5.1.34
Lineage    Species: Escherichia coli     (Click to Show/Hide the Complete Species Lineage)
Kingdom: Bacteria
Phylum: Proteobacteria
Class: Gammaproteobacteria
Order: Enterobacterales
Family: Enterobacteriaceae
Genus: Escherichia
Species: Escherichia coli
Interactome
Disease Specific Interactions between Host Protein and DME (HOSPPI)
      Drug co-metabolism
               Cometabolized drug: Flunitrazepam Click to Show/Hide the Full List of HOSPPI:        6 HOSPPI
                            Cytochrome P450 1A2 (CYP1A2) Click to Show/Hide the Cometabolization Info
DME ID DME0003 DME Info
Uniprot ID
CP1A2_HUMAN
Interaction Name CYP1A2-nfsB interaction [1], [2]
Description The interaction, between human Cytochrome P450 1A2 and Oxygen-insensitive NADPH nitroreductase B from Escherichia coli which collectively metabolize the drug Flunitrazepam, is reported to affect the efficacy, safety or bioavailability of this drug via interfering with it metabolism.
                            Cytochrome P450 2A6 (CYP2A6) Click to Show/Hide the Cometabolization Info
DME ID DME0005 DME Info
Uniprot ID
CP2A6_HUMAN
Interaction Name CYP2A6-nfsB interaction [1], [3]
Description The interaction, between human Cytochrome P450 2A6 and Oxygen-insensitive NADPH nitroreductase B from Escherichia coli which collectively metabolize the drug Flunitrazepam, is reported to affect the efficacy, safety or bioavailability of this drug via interfering with it metabolism.
                            Cytochrome P450 2B6 (CYP2B6) Click to Show/Hide the Cometabolization Info
DME ID DME0020 DME Info
Uniprot ID
CP2B6_HUMAN
Interaction Name CYP2B6-nfsB interaction [1], [3]
Description The interaction, between human Cytochrome P450 2B6 and Oxygen-insensitive NADPH nitroreductase B from Escherichia coli which collectively metabolize the drug Flunitrazepam, 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-nfsB interaction [1], [3]
Description The interaction, between human Cytochrome P450 2C9 and Oxygen-insensitive NADPH nitroreductase B from Escherichia coli which collectively metabolize the drug Flunitrazepam, 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-nfsB interaction [1], [8]
Description The interaction, between human Cytochrome P450 3A4 and Oxygen-insensitive NADPH nitroreductase B from Escherichia coli which collectively metabolize the drug Flunitrazepam, is reported to affect the efficacy, safety or bioavailability of this drug via interfering with it metabolism.
                            Mephenytoin 4-hydroxylase (CYP2C19) Click to Show/Hide the Cometabolization Info
DME ID DME0021 DME Info
Uniprot ID
CP2CJ_HUMAN
Interaction Name CYP2C19-nfsB interaction [1], [10]
Description The interaction, between human Mephenytoin 4-hydroxylase and Oxygen-insensitive NADPH nitroreductase B from Escherichia coli which collectively metabolize the drug Flunitrazepam, 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-nfsB interaction [4], [5]
Description The interaction, between human Cytochrome P450 2D6 and Oxygen-insensitive NADPH nitroreductase B from Escherichia coli 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: Clonazepam Click to Show/Hide the Full List of HOSPPI:        2 HOSPPI
                            Cytochrome P450 3A4 (CYP3A4) Click to Show/Hide the Cometabolization Info
DME ID DME0001 DME Info
Uniprot ID
CP3A4_HUMAN
Interaction Name CYP3A4-nfsB interaction [6], [7]
Description The interaction, between human Cytochrome P450 3A4 and Oxygen-insensitive NADPH nitroreductase B from Escherichia coli which collectively metabolize the drug Clonazepam, is reported to affect the efficacy, safety or bioavailability of this drug via interfering with it metabolism.
                            RNA cytidine acetyltransferase (hALP) Click to Show/Hide the Cometabolization Info
DME ID DME0007 DME Info
Uniprot ID
NAT10_HUMAN
Interaction Name hALP-nfsB interaction [6], [14]
Description The interaction, between human RNA cytidine acetyltransferase and Oxygen-insensitive NADPH nitroreductase B from Escherichia coli which collectively metabolize the drug Clonazepam, is reported to affect the efficacy, safety or bioavailability of this drug via interfering with it metabolism.
               Cometabolized drug: Nitrazepam Click to Show/Hide the Full List of HOSPPI:        1 HOSPPI
                            Cytochrome P450 3A4 (CYP3A4) Click to Show/Hide the Cometabolization Info
DME ID DME0001 DME Info
Uniprot ID
CP3A4_HUMAN
Interaction Name CYP3A4-nfsB interaction [4], [9]
Description The interaction, between human Cytochrome P450 3A4 and Oxygen-insensitive NADPH nitroreductase B from Escherichia coli which collectively metabolize the drug Nitrazepam, is reported to affect the efficacy, safety or bioavailability of this drug via interfering with it metabolism.
               Cometabolized drug: Nitrobenzodiazepine 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-nfsB interaction [1], [11]
Description The interaction, between human NADPH-cytochrome P450 reductase and Oxygen-insensitive NADPH nitroreductase B from Escherichia coli which collectively metabolize the drug Nitrobenzodiazepine, is reported to affect the efficacy, safety or bioavailability of this drug via interfering with it metabolism.
               Cometabolized drug: CBL-954 Click to Show/Hide the Full List of HOSPPI:        1 HOSPPI
                            Quinone reductase 1 (NQO1) Click to Show/Hide the Cometabolization Info
DME ID DME0097 DME Info
Uniprot ID
NQO1_HUMAN
Interaction Name NQO1-nfsB interaction [4], [12], [13]
Description The interaction, between human Quinone reductase 1 and Oxygen-insensitive NADPH nitroreductase B from Escherichia coli which collectively metabolize the drug CBL-954, is reported to affect the efficacy, safety or bioavailability of this drug via interfering with it metabolism.
References
1 Structure-based development of bacterial nitroreductase against nitrobenzodiazepine-induced hypnosis. Biochem Pharmacol. 2012 Jun 15;83(12):1690-9.
2 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
3 CYP3A4 is the major CYP isoform mediating the in vitro hydroxylation and demethylation of flunitrazepam. Drug Metab Dispos. 2001 Feb;29(2):133-40.
4 Conversion of NfsB, a minor Escherichia coli nitroreductase, to a flavin reductase similar in biochemical properties to FRase I, the major flavin reductase in Vibrio fischeri, by a single amino acid substitution. J Bacteriol. 1996 Aug;178(15):4731-3.
5 Nefazodone pharmacokinetics in depressed children and adolescents. J Am Acad Child Adolesc Psychiatry. 2000 Aug;39(8):1008-16.
6 Characterization of Escherichia coli nitroreductase NfsB in the metabolism of nitrobenzodiazepines. Biochem Pharmacol. 2009 Jul 1;78(1):96-103.
7 Identification of the human and animal hepatic cytochromes P450 involved in clonazepam metabolism. Fundam Clin Pharmacol. 1993;7(2):69-75.
8 Cytochrome P450 3A4 and benzodiazepines. Seishin Shinkeigaku Zasshi. 2003;105(5):631-42.
9 Prediction of metabolic clearance using fresh human hepatocytes: comparison with cryopreserved hepatocytes and hepatic microsomes for five benzodiazepines. Xenobiotica. 2008 Apr;38(4):353-67.
10 The role of cytochrome P450 2C19 activity in flunitrazepam metabolism in vivo. J Clin Psychopharmacol. 2003 Apr;23(2):169-75.
11 Flavin-containing reductase: new perspective on the detoxification of nitrobenzodiazepine. Expert Opin Drug Metab Toxicol. 2010 Aug;6(8):967-81.
12 Discovery and evaluation of Escherichia coli nitroreductases that activate the anti-cancer prodrug CB1954. Biochem Pharmacol. 2010 Mar 1;79(5):678-87.
13 Gene Therapy of the Central Nervous System. Charter 22 - Prodrug-Activation Gene Therapy. 2006, Pages 291-301
14 Effect of common NAT2 variant alleles in the acetylation of the major clonazepam metabolite, 7-aminoclonazepam. Drug Metab Lett. 2007 Jan;1(1):3-5.

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