8RC9

W-formate dehydrogenase from Desulfovibrio vulgaris - Co-crystallized with Formate and Exposed to air for 2 h

Summary for 8RC9

• Entry DOI: 10.2210/pdb8rc9/pdb
• Related: 8RC8 8RCA 8RCB 8RCC
• Descriptor: Formate dehydrogenase, alpha subunit, selenocysteine-containing, Formate dehydrogenase, beta subunit, putative, 2-AMINO-5,6-DIMERCAPTO-7-METHYL-3,7,8A,9-TETRAHYDRO-8-OXA-1,3,9,10-TETRAAZA-ANTHRACEN-4-ONE GUANOSINE DINUCLEOTIDE, ... (10 entities in total)
• Functional Keywords: formate, co2, molybdenum and tungsten enzymes, dmso reductase family, electron transport, oxidoreductase
• Biological source: Desulfovibrio vulgaris str. Hildenborough; More
• Total number of polymer chains: 2
• Total formula weight: 139741.25

Authors

Vilela-Alves, G.,Manuel, R.R.,Pereira, I.C.,Romao, M.J.,Mota, C. (deposition date: 2023-12-06, release date: 2024-07-24, Last modification date: 2024-11-06)

Primary citation

Vilela-Alves, G.,Manuel, R.R.,Viegas, A.,Carpentier, P.,Biaso, F.,Guigliarelli, B.,Pereira, I.A.C.,Romao, M.J.,Mota, C.
Substrate-dependent oxidative inactivation of a W-dependent formate dehydrogenase involving selenocysteine displacement.
Chem Sci, 15:13090-13101, 2024

PubMed Abstract: Metal-dependent formate dehydrogenases are very promising targets for enzyme optimization and design of bio-inspired catalysts for CO 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 FdhAB (FdhAB) when exposed to oxygen in the presence of a substrate (formate or CO). This study reveals that O inactivation is promoted by the presence of either substrate and involves forming a different species in the active site, captured in the crystal structures, where the SeCys ligand is displaced from tungsten coordination and replaced by a dioxygen or peroxide molecule. This form was reproducibly obtained and supports the conclusion that, although W-FdhAB can catalyse the oxidation of formate in the presence of oxygen for some minutes, it gets irreversibly inactivated after prolonged O exposure in the presence of either substrate.

PubMed: 39148770
DOI: 10.1039/d4sc02394c

Experimental method

X-RAY DIFFRACTION (2.06 Å)