Identifying structural and dynamic changes during the Biliverdin Reductase B catalytic cycle.

Biliverdin Reductase B (BLVRB) is an NADPH-dependent reductase that catalyzes the reduction of multiple substrates and is therefore considered a critical cellular redox regulator. In this study, we sought to address whether both structural and dynamics changes occur between different intermediates of the catalytic cycle and whether these were relegated to just the active site or the entirety of the enzyme. Through X-ray crystallography, we determined the apo BLVRB structure for the first time, revealing subtle global changes compared to the holo structure and identifying the loss of a critical hydrogen bond that "clamps" the R78-loop over the coenzyme. Amide and Cα chemical shift perturbations were used to identify environmental and secondary structural changes between intermediates, with more distant global changes observed upon coenzyme binding compared to substrate interactions. NMR relaxation rate measurements provided insights into the dynamic behavior of BLVRB during the catalytic cycle. Specifically, the inherently dynamic R78-loop that becomes ordered upon coenzyme binding persists through the catalytic cycle while similar regions experience dynamic exchange. However, the dynamic exchange processes were found to differ through the catalytic cycle with several groups of residues exhibiting similar dynamic responses. Finally, both local and distal structural and dynamic changes occur within BLVRB that are dependent solely on the oxidative state of the coenzyme. Thus, through a comprehensive analysis here, this study revealed structural and dynamic alterations in BLVRB through its catalytic cycle that are not simply relegated to the active site, but instead, are allosterically coupled throughout the enzyme.

Are we failing female and racialized academics? A Canadian national survey examining the impacts of the COVID-19 pandemic on tenure and tenure-track faculty.

The novel coronavirus 2019 (COVID-19) pandemic caused the abrupt curtailment of on-campus research activities that amplified impacts experienced by female and racialized faculty. In this mixed-method study, we systematically and strategically unpack the impact of the shift of academic work environments to remote settings on tenured and tenure-track faculty in Canada. Our quantitative analysis demonstrated that female and racialized faculty experienced higher levels of stress, social isolation and lower well-being. Fewer women faculty felt support for health and wellness. Our qualitative data highlighted substantial gender inequities reported by female faculty such as increased caregiving burden that affected their research productivity. The most pronounced impacts were felt among pre-tenured female faculty. The present study urges university administration to take further action to support female and racialized faculty through substantial organizational change and reform. Given the disproportionate toll that female and racialized faculty experienced, we suggest a novel approach that include three dimensions of change: (1) establishing quantitative metrics to assess and evaluate pandemic-induced impact on research productivity, health and well-being, (2) coordinating collaborative responses with faculty unions across the nation to mitigate systemic inequities, and (3) strategically implementing a storytelling approach to amplify the experiences of marginalized populations such as women or racialized faculty and include those experiences as part of recommendations for change.