3TZB
Quinone Oxidoreductase (NQ02) bound to NSC13000
Summary for 3TZB
| Entry DOI | 10.2210/pdb3tzb/pdb |
| Descriptor | Ribosyldihydronicotinamide dehydrogenase [quinone], ZINC ION, FLAVIN-ADENINE DINUCLEOTIDE, ... (5 entities in total) |
| Functional Keywords | oxidoreductase, fad |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm: P16083 |
| Total number of polymer chains | 4 |
| Total formula weight | 107594.41 |
| Authors | Dunstan, M.S.,Leys, D. (deposition date: 2011-09-27, release date: 2011-11-02, Last modification date: 2024-02-28) |
| Primary citation | Nolan, K.A.,Dunstan, M.S.,Caraher, M.C.,Scott, K.A.,Leys, D.,Stratford, I.J. In silico screening reveals structurally diverse, nanomolar inhibitors of NQO2 that are functionally active in cells and can modulate NF-kappa B signaling. Mol.Cancer Ther., 11:194-203, 2012 Cited by PubMed Abstract: The National Cancer Institute chemical database has been screened using in silico docking to identify novel nanomolar inhibitors of NRH:quinone oxidoreductase 2 (NQO2). The inhibitors identified from the screen exhibit a diverse range of scaffolds and the structure of one of the inhibitors, NSC13000 cocrystalized with NQO2, has been solved. This has been used to aid the generation of a structure-activity relationship between the computationally derived binding affinity and experimentally measured enzyme inhibitory potency. Many of the compounds are functionally active as inhibitors of NQO2 in cells at nontoxic concentrations. To show this, advantage was taken of the NQO2-mediated toxicity of the chemotherapeutic drug CB1954. The toxicity of this drug is substantially reduced when the function of NQO2 is inhibited, and many of the compounds achieve this in cells at nanomolar concentrations. The NQO2 inhibitors also attenuated TNFα-mediated, NF-кB-driven transcriptional activity. The link between NQO2 and the regulation of NF-кB was confirmed by using short interfering RNA to NQO2 and by the observation that NRH, the cofactor for NQO2 enzyme activity, could regulate NF-кB activity in an NQO2-dependent manner. NF-кB is a potential therapeutic target and this study reveals an underlying mechanism that may be usable for developing new anticancer drugs. PubMed: 22090421DOI: 10.1158/1535-7163.MCT-11-0543 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1901 Å) |
Structure validation
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