8OK0

Crystal structure of human NQO1 in complex with the inhibitor PMSF

8OK0 の概要

• エントリーDOI: 10.2210/pdb8ok0/pdb
• 分子名称: NAD(P)H dehydrogenase [quinone] 1, FLAVIN-ADENINE DINUCLEOTIDE, phenylmethanesulfonic acid, ... (6 entities in total)
• 機能のキーワード: human nqo1, flavoenzyme, cancer, inhibitors, pmsf, flavoprotein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 127801.66

構造登録者

Martin-Garcia, J.M.,Grieco, A.,Ruiz-Fresneda, M.A. (登録日: 2023-03-26, 公開日: 2023-11-01, 最終更新日: 2023-11-22)

主引用文献

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

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: 37726177
DOI: 10.1002/1873-3468.14738

実験手法

X-RAY DIFFRACTION (1.6 Å)