Researchers from the Macromolecular Crystallography Lab at UCIBIO-NOVA FCT have recently published a study in the scientific journal Chemical Science, detailing critical steps toward optimizing metal-dependent formate dehydrogenases enzymes for carbon dioxide reduction, a promising strategy for climate change mitigation. The study, titled "Substrate-dependent oxidative inactivation of a W-dependent formate dehydrogenase involving selenocysteine displacement" offers insights that could lead to the development of more robust bio-inspired catalysts for biotechnological applications. This study was led by Cristiano Mota and Maria João Romão, in collaboration with Inês A. C. Pereira’s lab at ITQB-NOVA.
Guilherme Vilela-Alves, first author of the paper and PhD student at the Macromolecular Crystallography Lab, explained that "this study is crucial for advancing the understanding of the catalytic mechanisms and oxygen sensitivity of metal-dependent formate dehydrogenases. We aimed to understand how these enzymes, particularly Desulfovibrio vulgaris FdhAB, become inactivated by oxygen, and what was the role of the possible dissociation of the SeCys ligand from the Mo/W active site in this process”.
The research study involved a combination of biochemical, spectroscopic, and structural characterization of DvFdhAB. The enzyme was exposed to oxygen in the presence of formate or carbon dioxide, and crystal structures were analyzed to capture the changes in the active site. This multidisciplinary approach helped to identify the mechanism of oxygen inactivation and the role of the SeCys ligand in this process.
Cristiano Mota, senior researcher from the Macromolecular Crystallography Lab at UCIBIO-NOVA, explained: “The study revealed that oxygen inactivation of DvFdhAB is promoted by the presence of either formate or carbon dioxide, leading to the formation of a different species in the active site where the SeCys ligand is displaced from tungsten coordination and replaced by a dioxygen or peroxide molecule. Notably, it was observed for the first time that the enzyme is also inactivated in the presence of carbon dioxide and oxygen, and the reduction of the metal site was not necessary as previously proposed”.
Original article:
Substrate-dependent oxidative inactivation of a W-dependent formate dehydrogenase involving selenocysteine displacement
Guilherme Vilela-Alves, Rita R. Manuel, Aldino Viegas, Philippe Carpentier, Frédéric Biaso, Bruno Guigliarelli, Inês A. C. Pereira, Maria João Romão and Cristiano Mota.
Chemical Science, 2024
DOI: 10.1039/d4sc02394c