دورية أكاديمية
Structural dynamics at the active site of the cancer-associated flavoenzyme NQO1 probed by chemical modification with PMSF
| 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., Martín-García, José M. |
| المساهمون: | ALBA Synchrotron, Comunidad de Madrid, Ministerio de Ciencia, Innovación y Universidades (España), Junta de Andalucía, Ruiz-Fresneda, Miguel A., Pey, Angel L., Martín-García, José M. |
| بيانات النشر: | Federation of European Biochemical Societies |
| سنة النشر: | 2023 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| مصطلحات موضوعية: | PMSF, X-ray crystallography, Cancer, Flavoenzyme, Human NQO1 |
| الوصف: | 12 pags., 4 figs., 1 tab. ; 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. ; The X-ray diffraction experiments presented in this study were carried out at BL13-XALOC at ALBA syn-chrotron under proposal number 2020084437. The following funding is acknowledged: Ayuda de Atracción y Retención de Talento Investigador from the Community of Madrid (No. 2019-T1/BMD-15552); ERDF/Spanish Ministry of Science, Innovation and Universities—State Research Agency (Grant number RTI2018-096246-B-I00), Consejerıa de Economıa, Conocimiento Empresas y Universidad, Junta de Andalucía (Grant number P18-RT-2413), ERDF/Counseling of Economic transformation, Industry, Knowledge and Universities(Grant B-BIO-84-UGR20). ; Peer reviewed |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0014-5793 |
| العلاقة: | #PLACEHOLDER_PARENT_METADATA_VALUE#; 2019-T1/BMD-15552; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-096246-B-I00/ES/INTEGRANDO LAS MODIFICACIONES POSTRADUCCIONALES ESPECIFICAS DE SITIO EN ENFERMEDADES CONFORMACIONALES: MECANISMOS, EVOLUCION Y TERAPIAS/; FEBS letters; Publisher's version; https://doi.org/10.1002/1873-3468.14738Test; Sí; FEBS Letters 597(21): 2687-2698 (2023); http://hdl.handle.net/10261/344661Test; http://dx.doi.org/10.13039/501100011011Test; http://dx.doi.org/10.13039/100012818Test; 2-s2.0-85173549463; https://api.elsevier.com/content/abstract/scopus_id/85173549463Test |
| DOI: | 10.1002/1873-3468.14738 |
| DOI: | 10.13039/501100011011 |
| DOI: | 10.13039/100012818 |
| الإتاحة: | https://doi.org/10.1002/1873-3468.1473810.13039/50110001101110.13039/100012818Test http://hdl.handle.net/10261/344661Test https://api.elsevier.com/content/abstract/scopus_id/85173549463Test |
| حقوق: | open |
| رقم الانضمام: | edsbas.ADE1445 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00145793 |
|---|---|
| DOI: | 10.1002/1873-3468.14738 |