biostudies-literatureVilela-Alves GFundação para a Ciência e a TecnologiaAgence Nationale de la Recherche13090-13101https://www.ebi.ac.uk/biostudies/studies/S-EPMC11323313biostudies-literatureUnknown15(32)Metal-dependent formate dehydrogenases are very promising targets for enzyme optimization and design of bio-inspired catalysts for CO₂ reduction, towards innovative strategies for climate change mitigation. For effective application of these enzymes, the catalytic mechanism must be better understood, and the molecular determinants clarified. Despite numerous studies, several doubts persist, namely regarding the role played by the possible dissociation of the SeCys ligand from the Mo/W active site. Additionally, the oxygen sensitivity of these enzymes must also be understood as it poses an important obstacle for biotechnological applications. This work presents a combined biochemical, spectroscopic, and structural characterization of <i>Desulfovibrio vulgaris</i> FdhAB (<i>Dv</i>Chemical scienceSubstrate-dependent oxidative inactivation of a W-dependent formate dehydrogenase involving selenocysteine displacement.PMC11323313MOLYERE, 16-CE-29-0010-01UIDB/04378/2020LA/P/0140/2020UIDP/04612/2020UIDP/04378/2020UIDB/04612/2020PTDC/BII-BBF/2050/2020DFA/BD/7897/2020LA/P/0087/20202020.00043.CEECIND2023.00286.BDROTEIRO/0031/2013-PINFRA/22161/2016Romao MJManuel RRPereira IACMota CBiaso FGuigliarelli BVilela-Alves GViegas ACarpentier PfalseSubstrate-dependent oxidative inactivation of a W-dependent formate dehydrogenase involving selenocysteine displacement.Metal-dependent formate dehydrogenases are very promising targets for enzyme optimization and design of bio-inspired catalysts for CO₂ reduction, towards innovative strategies for climate change mitigation. For effective application of these enzymes, the catalytic mechanism must be better understood, and the molecular determinants clarified. Despite numerous studies, several doubts persist, namely regarding the role played by the possible dissociation of the SeCys ligand from the Mo/W active site. Additionally, the oxygen sensitivity of these enzymes must also be understood as it poses an important obstacle for biotechnological applications. This work presents a combined biochemical, spectroscopic, and structural characterization of <i>Desulfovibrio vulgaris</i> FdhAB (<i>Dv</i>2024-01-01T00:00:00Z2024 Aug2026-06-01T19:50:42.8Z2025-04-07T12:25:23.538ZS-EPMC113233133914877010.1039/d4sc02394c