The global Covid-19 pandemic has rapidly overwhelmed our societies, shocked the global economy and overburdened struggling health care systems and other social institutions around the world. While such impacts of Covid-19 are becoming clearer, the implications of the disease for energy and climate policy are more prosaic. This Special Section seeks to offer more clarity on the emerging connections between Covid-19 and energy supply and demand, energy governance, future low-carbon transitions, social justice, and even the practice of research methodology. It features articles that ask, and answer: What are the known and anticipated impacts of Covid-19 on energy demand and climate change? How has the disease shaped institutional responses and varying energy policy frameworks, especially in Africa? How will the disease impact ongoing social practices, innovations and sustainability transitions, including not only renewable energy but also mobility? How might the disease, and social responses to it, exacerbate underlying patterns of energy poverty, energy vulnerability, and energy injustice? Lastly, what challenges and insights does the pandemic offer for the
practice
of research, and for future research methodology? We find that without careful guidance and consideration, the brave new age wrought by Covid-19 could very well collapse in on itself with bloated stimulus packages that counter sustainability goals, misaligned incentives that exacerbate climate change, the entrenchment of unsustainable practices, and acute and troubling consequences for vulnerable groups.
alpha 1-Antitrypsin is a metastable and conformationally flexible protein that belongs to the serpin family of protease inhibitors. Although it is known that methionine oxidation in the protein's active site results in a loss of biological activity, there is little specific knowledge regarding the reactivity of each of the protein's methionine residues. In this study, we have used peptide mapping to study the oxidation kinetics of each of alpha 1-antitrypsin's methionines in alpha 1-AT((C232S)) as well as M351L and M358V mutants. These kinetic studies establish that Met1, Met226, Met242, Met351, and Met358 are reactive with hydrogen peroxide at neutral pH and that each reactive methionine is oxidized in a bimolecular, rather than coupled, mechanism. Analysis of Met226, Met351, and Met358 oxidation provides insights regarding the structure of alpha 1-antitrypsin's active site that allow us to relate conformation to experimentally observed reactivity. The relationship between solution pH and methionine oxidation was also examined to evaluate methionine reactivity under conditions that perturb the native structure. Methionine oxidation data show that at pH 5, global conformational changes occur that alter the oxidation susceptibility of each of alpha 1-antitrypsin's 10 methionine residues. Between pH 6 and 9, however, more localized conformational changes occur that affect primarily the reactivity of Met242. In sum, this work provides a detailed analysis of methionine oxidation in alpha 1-antitrypsin and offers new insights into the protein's solution structure.
Oxidative damage to the sulfur-containing amino acids, methionine and cysteine, is a major concern in biotechnology and medicine. ␣1-Antitrypsin, which is a metastable and conformationally flexible protein that belongs to the serpin family of protease inhibitors, contains nine methionines and a single cysteine in its primary sequence. Although it is known that methionine oxidation in the protein active site results in a loss of biological activity, there is little specific knowledge regarding the reactivity of its unpaired thiol, Cys-232. In this study, the thiol-modifying reagent NBD-Cl (7-chloro-4-nitrobenz-2-oxa-1,3-diazole) was used to label peroxide-modified ␣1-antitrypsin and demonstrate that the Cys-232 in vitro oxidation pathway begins with a stable sulfenic acid intermediate and is followed by the formation of sulfinic and cysteic acid in successive steps. pH-dependent reactivity with hydrogen peroxide showed that Cys-232 has a pK a of 6.86 ؎ 0.05, a value that is more than 1.5 pH units lower than that of a typical protein thiol. pH-induced conformational changes in the region surrounding Cys-232 were also examined and indicate that mildly acidic conditions induce a conformation that enhances Cys-232 reactivity. In summary, this work provides new insights into ␣1-antitrypsin reactivity in oxidizing environments and shows that a unique structural environment renders its unpaired thiol, Cys-232, its most reactive amino acid.
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