Publicação
Substrate-dependent oxidative inactivation of a W-dependent formate dehydrogenase involving selenocysteine displacement
| Resumo: | 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 Desulfovibrio vulgaris FdhAB (DvFdhAB) when exposed to oxygen in the presence of a substrate (formate or CO2). This study reveals that O2 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-DvFdhAB can catalyse the oxidation of formate in the presence of oxygen for some minutes, it gets irreversibly inactivated after prolonged O2 exposure in the presence of either substrate. |
|---|---|
| Autores principais: | Vilela-Alves, Guilherme |
| Outros Autores: | Manuel, Rita R.; Viegas, Aldino; Carpentier, Philippe; Biaso, Frédéric; Guigliarelli, Bruno; Pereira, Inês A.C.; Romão, Maria João; Mota, Cristiano |
| Assunto: | General Chemistry SDG 13 - Climate Action |
| Ano: | 2024 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade Nova de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Institucional da UNL |
| _version_ | 1868983431160922112 |
|---|---|
| author | Vilela-Alves, Guilherme |
| author2 | Manuel, Rita R. Viegas, Aldino Carpentier, Philippe Biaso, Frédéric Guigliarelli, Bruno Pereira, Inês A.C. Romão, Maria João Mota, Cristiano |
| author2_role | author author author author author author author author |
| author_facet | Vilela-Alves, Guilherme Manuel, Rita R. Viegas, Aldino Carpentier, Philippe Biaso, Frédéric Guigliarelli, Bruno Pereira, Inês A.C. Romão, Maria João Mota, Cristiano |
| author_role | author |
| contributor_name_str_mv | Faculdade de Ciências e Tecnologia (FCT) UCIBIO - Applied Molecular Biosciences Unit Instituto de Tecnologia Química e Biológica António Xavier (ITQB) ROYAL SOC CHEMISTRY RUN |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Vilela-Alves, Guilherme\"},{\"Person.name\":\"Manuel, Rita R.\"},{\"Person.name\":\"Viegas, Aldino\"},{\"Person.name\":\"Carpentier, Philippe\"},{\"Person.name\":\"Biaso, Frédéric\"},{\"Person.name\":\"Guigliarelli, Bruno\"},{\"Person.name\":\"Pereira, Inês A.C.\"},{\"Person.name\":\"Romão, Maria João\"},{\"Person.name\":\"Mota, Cristiano\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Faculdade de Ciências e Tecnologia (FCT) UCIBIO - Applied Molecular Biosciences Unit Instituto de Tecnologia Química e Biológica António Xavier (ITQB) ROYAL SOC CHEMISTRY RUN |
| datacite.creators.creator.creatorName.fl_str_mv | Vilela-Alves, Guilherme Manuel, Rita R. Viegas, Aldino Carpentier, Philippe Biaso, Frédéric Guigliarelli, Bruno Pereira, Inês A.C. Romão, Maria João Mota, Cristiano |
| datacite.date.Accepted.fl_str_mv | 2024-08-14T00:00:00Z |
| datacite.date.available.fl_str_mv | 2025-05-07T21:20:03Z |
| datacite.date.embargoed.fl_str_mv | 2025-05-07T21:20:03Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | General Chemistry SDG 13 - Climate Action |
| datacite.titles.title.fl_str_mv | Substrate-dependent oxidative inactivation of a W-dependent formate dehydrogenase involving selenocysteine displacement |
| dc.contributor.none.fl_str_mv | Faculdade de Ciências e Tecnologia (FCT) UCIBIO - Applied Molecular Biosciences Unit Instituto de Tecnologia Química e Biológica António Xavier (ITQB) ROYAL SOC CHEMISTRY RUN |
| dc.creator.none.fl_str_mv | Vilela-Alves, Guilherme Manuel, Rita R. Viegas, Aldino Carpentier, Philippe Biaso, Frédéric Guigliarelli, Bruno Pereira, Inês A.C. Romão, Maria João Mota, Cristiano |
| dc.date.Accepted.fl_str_mv | 2024-08-14T00:00:00Z |
| dc.date.available.fl_str_mv | 2025-05-07T21:20:03Z |
| dc.date.embargoed.fl_str_mv | 2025-05-07T21:20:03Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10362/182755 |
| dc.language.none.fl_str_mv | eng |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | General Chemistry SDG 13 - Climate Action |
| dc.title.fl_str_mv | Substrate-dependent oxidative inactivation of a W-dependent formate dehydrogenase involving selenocysteine displacement |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | 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 Desulfovibrio vulgaris FdhAB (DvFdhAB) when exposed to oxygen in the presence of a substrate (formate or CO2). This study reveals that O2 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-DvFdhAB can catalyse the oxidation of formate in the presence of oxygen for some minutes, it gets irreversibly inactivated after prolonged O2 exposure in the presence of either substrate. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://run.unl.pt/bitstreams/162d15d1-e6fc-48bf-a11c-211656acae0c/download |
| id | run_a3bd85f8a143beb2bf1b8e9f1e882f2d |
| identifier.url.fl_str_mv | http://hdl.handle.net/10362/182755 |
| inst_facet_str | urn:organizationAcronym:unl{{{_:::_}}}Universidade Nova de Lisboa |
| instacron_str | unl |
| institution | Universidade Nova de Lisboa |
| instname_str | Universidade Nova de Lisboa |
| language | eng |
| network_acronym_str | run |
| network_name_str | Repositório Institucional da UNL |
| oai_identifier_str | oai:run.unl.pt:10362/182755 |
| organization_str_mv | urn:organizationAcronym:unl |
| person_str_mv | Vilela-Alves, Guilherme Manuel, Rita R. Viegas, Aldino Carpentier, Philippe Biaso, Frédéric Guigliarelli, Bruno Pereira, Inês A.C. Romão, Maria João Mota, Cristiano |
| publishDate | 2024 |
| repo_facet_str | urn:repositoryAcronym:run{{{_:::_}}}Repositório Institucional da UNL |
| reponame_str | Repositório Institucional da UNL |
| repository_id_str | urn:repositoryAcronym:run |
| service_str_mv | urn:repositoryAcronym:run |
| spelling | engenMetal-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 Desulfovibrio vulgaris FdhAB (DvFdhAB) when exposed to oxygen in the presence of a substrate (formate or CO2). This study reveals that O2 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-DvFdhAB can catalyse the oxidation of formate in the presence of oxygen for some minutes, it gets irreversibly inactivated after prolonged O2 exposure in the presence of either substrate.application/pdfenSubstrate-dependent oxidative inactivation of a W-dependent formate dehydrogenase involving selenocysteine displacementVilela-Alves, GuilhermeManuel, Rita R.Viegas, AldinoCarpentier, PhilippeBiaso, FrédéricGuigliarelli, BrunoPereira, Inês A.C.Romão, Maria JoãoMota, CristianoFaculdade de Ciências e Tecnologia (FCT)UCIBIO - Applied Molecular Biosciences UnitInstituto de Tecnologia Química e Biológica António Xavier (ITQB)ROYAL SOC CHEMISTRYHostingInstitutionOrganizationalRUNe-mailmailto:run@unl.ptrun@unl.ptISSNIsPartOf2041-6520URNIsPartOfPURE: 99997349URNIsPartOfPURE UUID: 81d2b972-3c1c-4a34-8cff-ce3dee6606a1URNIsPartOfScopus: 85199534626URNIsPartOfORCID: /0000-0002-3004-0543/work/183499873URNIsPartOfORCID: /0000-0002-8999-0420/work/183500013DOIIsPartOf10.1039/d4sc02394c2025-05-07T21:20:03Z2024-08-142024-08-14T00:00:00ZHandlehttp://hdl.handle.net/10362/182755http://purl.org/coar/access_right/c_abf2open accessGeneral ChemistrySDG 13 - Climate Action20001335 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://run.unl.pt/bitstreams/162d15d1-e6fc-48bf-a11c-211656acae0c/download |
| spellingShingle | Substrate-dependent oxidative inactivation of a W-dependent formate dehydrogenase involving selenocysteine displacement Vilela-Alves, Guilherme General Chemistry SDG 13 - Climate Action |
| status | SINGLETON |
| subject.fl_str_mv | General Chemistry SDG 13 - Climate Action |
| title | Substrate-dependent oxidative inactivation of a W-dependent formate dehydrogenase involving selenocysteine displacement |
| title_full | Substrate-dependent oxidative inactivation of a W-dependent formate dehydrogenase involving selenocysteine displacement |
| title_fullStr | Substrate-dependent oxidative inactivation of a W-dependent formate dehydrogenase involving selenocysteine displacement |
| title_full_unstemmed | Substrate-dependent oxidative inactivation of a W-dependent formate dehydrogenase involving selenocysteine displacement |
| title_short | Substrate-dependent oxidative inactivation of a W-dependent formate dehydrogenase involving selenocysteine displacement |
| title_sort | Substrate-dependent oxidative inactivation of a W-dependent formate dehydrogenase involving selenocysteine displacement |
| topic | General Chemistry SDG 13 - Climate Action |
| topic_facet | General Chemistry SDG 13 - Climate Action |
| url | http://hdl.handle.net/10362/182755 |
| visible | 1 |