8OK0
Crystal structure of human NQO1 in complex with the inhibitor PMSF
Summary for 8OK0
| Entry DOI | 10.2210/pdb8ok0/pdb |
| Descriptor | NAD(P)H dehydrogenase [quinone] 1, FLAVIN-ADENINE DINUCLEOTIDE, phenylmethanesulfonic acid, ... (6 entities in total) |
| Functional Keywords | human nqo1, flavoenzyme, cancer, inhibitors, pmsf, flavoprotein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 4 |
| Total formula weight | 127801.66 |
| Authors | Martin-Garcia, J.M.,Grieco, A.,Ruiz-Fresneda, M.A. (deposition date: 2023-03-26, release date: 2023-11-01, Last modification date: 2023-11-22) |
| Primary citation | Grieco, A.,Ruiz-Fresneda, M.A.,Gomez-Mulas, A.,Pacheco-Garcia, J.L.,Quereda-Moraleda, I.,Pey, A.L.,Martin-Garcia, J.M. Structural dynamics at the active site of the cancer-associated flavoenzyme NQO1 probed by chemical modification with PMSF. Febs Lett., 597:2687-2698, 2023 Cited by PubMed Abstract: A large conformational heterogeneity of human NAD(P)H:quinone oxidoreductase 1 (NQO1), a flavoprotein associated with various human diseases, has been observed to occur in the catalytic site of the enzyme. Here, we report the X-ray structure of NQO1 with phenylmethylsulfonyl fluoride (PMSF) at 1.6 Å resolution. Activity assays confirmed that, despite being covalently bound to the Tyr128 residue at the catalytic site, PMSF did not abolish NQO1 activity. This may indicate that the PMSF molecule does not reduce the high flexibility of Tyr128, thus allowing NADH and DCPIP substrates to bind to the enzyme. Our results show that targeting Tyr128, a key residue in NQO1 function, with small covalently bound molecules could possibly not be a good drug discovery strategy to inhibit this enzyme. PubMed: 37726177DOI: 10.1002/1873-3468.14738 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.6 Å) |
Structure validation
Download full validation report
