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Structural Insights Into CO2 Transport Pathways in a W-Formate Dehydrogenase

2026-04-13Artigo científico Acesso aberto
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dc.contributor.authorVilela-Alves, Guilherme
dc.contributor.authorManuel, Rita Rebelo
dc.contributor.authorMartins, Guilherme
dc.contributor.authorCarpentier, Philippe
dc.contributor.authorRaczyńska, Agata
dc.contributor.authorSzaleniec, Maciej
dc.contributor.authorPereira, Inês A.Cardoso
dc.contributor.authorRomão, Maria João
dc.contributor.authorMota, Cristiano
dc.contributor.institutionDQ - Departamento de Química
dc.contributor.institutionUCIBIO - Applied Molecular Biosciences Unit
dc.contributor.institutionInstituto de Tecnologia Química e Biológica António Xavier (ITQB)
dc.contributor.pblJohn Wiley & Sons, Ltd.
dc.date.accessioned2026-07-22T08:46:01Z
dc.date.available2026-07-22T08:46:01Z
dc.date.issued2026-04-13
dc.descriptionWe acknowledgethe European Synchrotron Radiation Facility for provision of synchrotronradiation facilities, and we would like to thank the staff of the ESRF andEMBL Grenoble for assistance and support in using beamlines ID23-1, ID23-2, ID30A-3, and ID30B. Development of AMBER parameters forMD simulations was supported by the European Union’s HORIZON-EIC-2023- PATHFINDEROPEN-01 project W-BioCat. We also acknowledgeJoão Carita for the technical input and work on N. vulgaris cellgrowths. We gratefully acknowledge Polish high-performance computinginfrastructure PLGrid (HPC Centres: ACK Cyfronet AGH) for provid-ing computer facilities and support within computational grant nos.PLG/2025/018297 and PLG/2025/018449. Open access publication funding provided by FCT (b-on). Publisher Copyright: © 2026 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.
dc.description.abstractMo/W-dependent formate dehydrogenases (Fdhs) catalyze the reversible reduction of CO2 to formate and are key biocatalysts with high potential for CO2 capture/conversion technologies. Although previous studies have suggested the presence of two substrate-access tunnels in Fdhs, experimental evidence for CO2-specific pathways has been lacking. Here, we present an integrated study of Nitratidesulfovibrio vulgaris FdhAB combining crystallography, molecular dynamics simulations, mutagenesis, and kinetic assays. NvFdhAB crystals pressurized with Kr, O2, and CO2 were used to map gas diffusion routes and uncovered a substrate-retention site consistently occupied by small molecules in multiple crystal structures. Our results indicate that both substrates mostly use the main tunnel to reach this retention site, but H2O and CO2 can also enter through a novel side branch before following a shared route to the buried W active site. The retention site, located at the junction of both tunnels, plays a synergistic role in enhancing CO2 reduction by increasing substrate concentration near the catalytic center, thereby improving catalytic efficiency. Notably, variants affecting this site showed a selective effect for CO2 reduction, with no impact on formate oxidation. These findings provide experimental evidence of a CO2-specific pathway and identify structural determinants underpinning efficient CO2 reduction in this enzyme family.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent3733118
dc.identifier.doi10.1002/anie.202526133
dc.identifier.issn1433-7851
dc.identifier.otherPURE: 169069579
dc.identifier.otherPURE UUID: ab0f76b3-a4df-4593-b632-b34a7aedadb9
dc.identifier.otherScopus: 105032150801
dc.identifier.otherPubMed: 41787858
dc.identifier.otherORCID: /0000-0002-3004-0543/work/221523503
dc.identifier.otherORCID: /0000-0002-8999-0420/work/221523734
dc.identifier.urihttp://hdl.handle.net/10362/204734
dc.identifier.urlhttps://www.scopus.com/pages/publications/105032150801
dc.language.isoeng
dc.peerreviewedyes
dc.relationinfo:eu-repo/grantAgreement/FCT//2023.00286.BD/PT
dc.relationinfo:eu-repo/grantAgreement/FCT//2020.07897.BD/PT
dc.relationinfo:eu-repo/grantAgreement/FCT/Concurso para Financiamento de Projetos de Investigação Científica e Desenvolvimento Tecnológico em Todos os Domínios Científicos - 2020/PTDC%2FBII-BBF%2F2050%2F2020/PT
dc.relationinfo:eu-repo/grantAgreement/FCT/Concurso de Projetos de IC&DT em Todos os Domínios Científicos 2023/2023.18077.ICDT/PT
dc.relationinfo:eu-repo/grantAgreement/FCT/Concurso de avaliação no âmbito do Programa Plurianual de Financiamento de Unidades de I&D (2017%2F2018) - Financiamento Programático/UIDP%2F04378%2F2020/PT
dc.relationinfo:eu-repo/grantAgreement/FCT/Concurso de avaliação no âmbito do Programa Plurianual de Financiamento de Unidades de I&D (2017%2F2018) - Financiamento Base/UIDB%2F04378%2F2020/PT
dc.relationinfo:eu-repo/grantAgreement/FCT/Concurso de avaliação no âmbito do Programa Plurianual de Financiamento de Unidades de I&D (2017%2F2018) - Financiamento Base/UIDB%2F04612%2F2020/PT
dc.relationinfo:eu-repo/grantAgreement/FCT/Concurso de avaliação no âmbito do Programa Plurianual de Financiamento de Unidades de I&D (2017%2F2018) - Financiamento Programático/UIDP%2F04612%2F2020/PT
dc.relationinfo:eu-repo/grantAgreement/FCT/Concurso para Atribuição do Estatuto e Financiamento de Laboratórios Associados (LA)/LA%2FP%2F0140%2F2020/PT
dc.relationinfo:eu-repo/grantAgreement/FCT/Concurso para Atribuição do Estatuto e Financiamento de Laboratórios Associados (LA)/LA%2FP%2F0087%2F2020/PT
dc.subjectCO reduction
dc.subjectgas soaking
dc.subjectmetal-dependent formate dehydrogenases
dc.subjectsubstrate tunnel
dc.subjectx-ray crystallography
dc.subjectCatalysis
dc.subjectGeneral Chemistry
dc.titleStructural Insights Into CO2 Transport Pathways in a W-Formate Dehydrogenaseen
dc.title.subtitleStructural Basis for CO2 Reductionen
dc.typejournal article
degois.publication.issue16
degois.publication.titleAngewandte Chemie - International Edition
degois.publication.volume65
dspace.entity.typePublication
rcaap.rightsopenAccess

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