التفاصيل البيبلوغرافية
| العنوان: |
Structural dynamics at the active site of the cancer‐associated flavoenzyme NQO1 probed by chemical modification with PMSF |
| المؤلفون: |
Grieco, Alice, Ruiz‐Fresneda, Miguel A., Gómez‐Mulas, Atanasio, Pacheco‐García, Juan Luis, Quereda‐Moraleda, Isabel, Pey, Angel L., Martin‐Garcia, Jose M. |
| المساهمون: |
Comunidad de Madrid, Consejería de Economía, Conocimiento, Empresas y Universidad, Junta de Andalucía, Ministerio de Ciencia e Innovación |
| المصدر: |
FEBS Letters ; volume 597, issue 21, page 2687-2698 ; ISSN 0014-5793 1873-3468 |
| بيانات النشر: |
Wiley |
| سنة النشر: |
2023 |
| المجموعة: |
Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: |
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. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1002/1873-3468.14738 |
| الإتاحة: |
https://doi.org/10.1002/1873-3468.14738Test |
| حقوق: |
http://creativecommons.org/licenses/by-nc-nd/4.0Test/ |
| رقم الانضمام: |
edsbas.89E82AED |
| قاعدة البيانات: |
BASE |
