Structural highlights
3te7 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
|
| Ligands: | , , , |
| Gene: | NQO2, NMOR2 (HUMAN) |
| Activity: | Ribosyldihydronicotinamide dehydrogenase (quinone), with EC number 1.10.99.2 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[NQO2_HUMAN] The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinones involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis.[1]
Publication Abstract from PubMed
Imidazoacridin-6-ones are shown to be potent nanomolar inhibitors of the enzyme NQO2. By use of computational molecular modeling, a reliable QSAR was established, relating inhibitory potency with calculated binding affinity. Further, crystal structures of NQO2 containing two of the imidazoacridin-6-ones have been solved. To generate compounds with reduced off-target (DNA binding) effects, an N-oxide moiety was introduced into the tertiary aminoalkyl side chain of the imidazoacridin-6-ones. This resulted in substantially less toxicity in a panel of eight cancer cell lines, decreased protein binding, and reduced DNA binding and nuclear accumulation. Finally, one of the N-oxides showed potent ability to inhibit the enzymatic function of NQO2 in cells, and therefore, it may be useful as a pharmacological probe to study the properties of the enzyme in vitro and in vivo.
Novel Inhibitors of NRH:Quinone Oxidoreductase 2 (NQO2): Crystal Structures, Biochemical Activity, and Intracellular Effects of Imidazoacridin-6-ones.,Dunstan MS, Barnes J, Humphries M, Whitehead RC, Bryce RA, Leys D, Stratford IJ, Nolan KA J Med Chem. 2011 Sep 13. PMID:21859103[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Calamini B, Santarsiero BD, Boutin JA, Mesecar AD. Kinetic, thermodynamic and X-ray structural insights into the interaction of melatonin and analogues with quinone reductase 2. Biochem J. 2008 Jul 1;413(1):81-91. PMID:18254726 doi:10.1042/BJ20071373
- ↑ Dunstan MS, Barnes J, Humphries M, Whitehead RC, Bryce RA, Leys D, Stratford IJ, Nolan KA. Novel Inhibitors of NRH:Quinone Oxidoreductase 2 (NQO2): Crystal Structures, Biochemical Activity, and Intracellular Effects of Imidazoacridin-6-ones. J Med Chem. 2011 Sep 13. PMID:21859103 doi:10.1021/jm200416e
