During the COVID-19 pandemic, the structural biology community swung into action quickly and efficiently, and many urgent questions were solved by macromolecular structure determination. The Coronavir Show more
During the COVID-19 pandemic, the structural biology community swung into action quickly and efficiently, and many urgent questions were solved by macromolecular structure determination. The Coronavirus Structural Task Force evaluated all structures from SARS-CoV-1 and SARS-CoV-2, but errors in measurement, data processing and modelling are present beyond these structures and throughout the structures deposited in the Protein Data Bank. Identifying them is only the first step; in order to minimize the impact that errors have in structural biology, error culture needs to change. It should be emphasized that the atomic model which is published is an interpretation of the measurement. Furthermore, risks should be minimized by addressing issues early and by investigating the source of a given problem, so that it may be avoided in the future. If we as a community can do this, it will greatly benefit experimental structural biologists as well as downstream users who are using structural models to deduce new biological and medical answers in the future. Show less
2022 · Life Sciences · Elsevier · added 2026-04-21
The Nrf2 transcription factor governs the expression of hundreds genes involved in cell defense against oxidative stress, the hallmark of numerous diseases such as neurodegenerative, cardiovascular, s Show more
The Nrf2 transcription factor governs the expression of hundreds genes involved in cell defense against oxidative stress, the hallmark of numerous diseases such as neurodegenerative, cardiovascular, some viral pathologies, diabetes and others. The main route for Nrf2 activity regulation is via interactions with the Keap1 protein. Under the normoxia the Keap1 binds the Nrf2 and targets it to the proteasomal degradation, while the Keap1 is regenerated. Upon oxidative stress the interactions between Nrf2 and Keap1 are interrupted and the Nrf2 activates the transcription of the protective genes. Currently, the Nrf2 system activation is considered as a powerful cytoprotective strategy for treatment of different pathologies, which pathogenesis relies on oxidative stress including viral diseases of pivotal importance such as COVID-19. The implementation of this strategy is accomplished mainly through the inactivation of the Keap1 "guardian" function. Two approaches are now developing: the Keap1 modification via electrophilic agents, which leads to the Nrf2 release, and direct interruption of the Nrf2:Keap1 protein-protein interactions (PPI). Because of theirs chemical structure, the Nrf2 electrophilic inducers could non-specifically interact with others cellular proteins leading to undesired effects. Whereas the non-electrophilic inhibitors of the Nrf2:Keap1 PPI could be more specific, thereby widening the therapeutic window. Show less