Unveiling the membrane bound dihydroorotate

Detalhes bibliográficos
Autor(a) principal: Sousa, Filipe M.
Data de Publicação: 2023
Outros Autores: Pires, Patrícia, Barreto, Andreia, Refojo, Patrícia N., Silva, Micael S., Fernandes, Pedro B., Carapeto, Ana P., Robalo, Tiago T., Rodrigues, Mário S., Pinho, Mariana G., Cabrita, Eurico J., Pereira, Manuela M.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/158656
Resumo: Funding Information: Helena Gaspar is acknowledged for the HPLC analyses and Bruno Victor for advice on modelling. F.M.S. and M.S.S. are recipients of fellowships by Fundação para a Ciência e a Tecnologia (PD/BD/128213/2016 and PD/BD/128202/2016, respectively, both within the scope of the PhD program Molecular Biosciences PD/00133/2012). A.B. is recipient of a fellowship by Fundação para a Ciência e a Tecnologia UI/BD/153052/2022. The work was funded by Fundação para a Ciência e a Tecnologia ( PTDC/BIA-BQM/2599/2021 to M.M.P). The project was further supported by UIDB/04046/2020 and UIDP/04046/2020 Centre grants from FCT , Portugal (to BioISI), by LISBOA-01-0145-FEDER-007660 cofunded by FEDER through COMPETE2020-POCI and by Fundação para a Ciência e a Tecnologia and by UIDB/04612/2020 and UIDP/04612/2020 research unit grants from FCT (to Mostmicro). The NMR spectrometers are part of the National NMR Network (PTNMR) and are supported by Infrastructure Project N° 022161 (co-financed by FEDER through COMPETE 2020, POCI, and PORL and FCT through PIDDAC). Funding Information: Helena Gaspar is acknowledged for the HPLC analyses and Bruno Victor for advice on modelling. F.M.S. and M.S.S. are recipients of fellowships by Fundação para a Ciência e a Tecnologia (PD/BD/128213/2016 and PD/BD/128202/2016, respectively, both within the scope of the PhD program Molecular Biosciences PD/00133/2012). A.B. is recipient of a fellowship by Fundação para a Ciência e a Tecnologia UI/BD/153052/2022. The work was funded by Fundação para a Ciência e a Tecnologia (PTDC/BIA-BQM/2599/2021 to M.M.P). The project was further supported by UIDB/04046/2020 and UIDP/04046/2020 Centre grants from FCT, Portugal (to BioISI), by LISBOA-01-0145-FEDER-007660 cofunded by FEDER through COMPETE2020-POCI and by Fundação para a Ciência e a Tecnologia and by UIDB/04612/2020 and UIDP/04612/2020 research unit grants from FCT (to Mostmicro). The NMR spectrometers are part of the National NMR Network (PTNMR) and are supported by Infrastructure Project N° 022161 (co-financed by FEDER through COMPETE 2020, POCI, and PORL and FCT through PIDDAC). Publisher Copyright: © 2022 The Author(s)
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spelling Unveiling the membrane bound dihydroorotateQuinone oxidoreductase from Staphylococcus aureusBacterial respirationDHODHelectron transferFlavoproteinFMNQuinoneRespiratory chainStaphylococcus aureusBiophysicsBiochemistryCell BiologyFunding Information: Helena Gaspar is acknowledged for the HPLC analyses and Bruno Victor for advice on modelling. F.M.S. and M.S.S. are recipients of fellowships by Fundação para a Ciência e a Tecnologia (PD/BD/128213/2016 and PD/BD/128202/2016, respectively, both within the scope of the PhD program Molecular Biosciences PD/00133/2012). A.B. is recipient of a fellowship by Fundação para a Ciência e a Tecnologia UI/BD/153052/2022. The work was funded by Fundação para a Ciência e a Tecnologia ( PTDC/BIA-BQM/2599/2021 to M.M.P). The project was further supported by UIDB/04046/2020 and UIDP/04046/2020 Centre grants from FCT , Portugal (to BioISI), by LISBOA-01-0145-FEDER-007660 cofunded by FEDER through COMPETE2020-POCI and by Fundação para a Ciência e a Tecnologia and by UIDB/04612/2020 and UIDP/04612/2020 research unit grants from FCT (to Mostmicro). The NMR spectrometers are part of the National NMR Network (PTNMR) and are supported by Infrastructure Project N° 022161 (co-financed by FEDER through COMPETE 2020, POCI, and PORL and FCT through PIDDAC). Funding Information: Helena Gaspar is acknowledged for the HPLC analyses and Bruno Victor for advice on modelling. F.M.S. and M.S.S. are recipients of fellowships by Fundação para a Ciência e a Tecnologia (PD/BD/128213/2016 and PD/BD/128202/2016, respectively, both within the scope of the PhD program Molecular Biosciences PD/00133/2012). A.B. is recipient of a fellowship by Fundação para a Ciência e a Tecnologia UI/BD/153052/2022. The work was funded by Fundação para a Ciência e a Tecnologia (PTDC/BIA-BQM/2599/2021 to M.M.P). The project was further supported by UIDB/04046/2020 and UIDP/04046/2020 Centre grants from FCT, Portugal (to BioISI), by LISBOA-01-0145-FEDER-007660 cofunded by FEDER through COMPETE2020-POCI and by Fundação para a Ciência e a Tecnologia and by UIDB/04612/2020 and UIDP/04612/2020 research unit grants from FCT (to Mostmicro). The NMR spectrometers are part of the National NMR Network (PTNMR) and are supported by Infrastructure Project N° 022161 (co-financed by FEDER through COMPETE 2020, POCI, and PORL and FCT through PIDDAC). Publisher Copyright: © 2022 The Author(s)Staphylococcus aureus is an opportunistic pathogen and one of the most frequent causes for community acquired and nosocomial bacterial infections. Even so, its energy metabolism is still under explored and its respiratory enzymes have been vastly overlooked. In this work, we unveil the dihydroorotate:quinone oxidoreductase (DHOQO) from S. aureus, the first example of a DHOQO from a Gram-positive organism. This protein was shown to be a FMN containing menaquinone reducing enzyme, presenting a Michaelis-Menten behaviour towards the two substrates, which was inhibited by Brequinar, Leflunomide, Lapachol, HQNO, Atovaquone and TFFA with different degrees of effectiveness. Deletion of the DHOQO coding gene (Δdhoqo) led to lower bacterial growth rates, and effected in cell morphology and metabolism, most importantly in the pyrimidine biosynthesis, here systematized for S. aureus MW2 for the first time. This work unveils the existence of a functional DHOQO in the respiratory chain of the pathogenic bacterium S. aureus, enlarging the understanding of its energy metabolism.Instituto de Tecnologia Química e Biológica António Xavier (ITQB)UCIBIO - Applied Molecular Biosciences UnitDQ - Departamento de QuímicaFaculdade de Ciências e Tecnologia (FCT)RUNSousa, Filipe M.Pires, PatríciaBarreto, AndreiaRefojo, Patrícia N.Silva, Micael S.Fernandes, Pedro B.Carapeto, Ana P.Robalo, Tiago T.Rodrigues, Mário S.Pinho, Mariana G.Cabrita, Eurico J.Pereira, Manuela M.2023-10-03T22:19:19Z2023-04-012023-04-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/158656eng0005-2728PURE: 72696123https://doi.org/10.1016/j.bbabio.2022.148948info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:41:12Zoai:run.unl.pt:10362/158656Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:57:15.384945Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Unveiling the membrane bound dihydroorotate
Quinone oxidoreductase from Staphylococcus aureus
title Unveiling the membrane bound dihydroorotate
spellingShingle Unveiling the membrane bound dihydroorotate
Sousa, Filipe M.
Bacterial respiration
DHODH
electron transfer
Flavoprotein
FMN
Quinone
Respiratory chain
Staphylococcus aureus
Biophysics
Biochemistry
Cell Biology
title_short Unveiling the membrane bound dihydroorotate
title_full Unveiling the membrane bound dihydroorotate
title_fullStr Unveiling the membrane bound dihydroorotate
title_full_unstemmed Unveiling the membrane bound dihydroorotate
title_sort Unveiling the membrane bound dihydroorotate
author Sousa, Filipe M.
author_facet Sousa, Filipe M.
Pires, Patrícia
Barreto, Andreia
Refojo, Patrícia N.
Silva, Micael S.
Fernandes, Pedro B.
Carapeto, Ana P.
Robalo, Tiago T.
Rodrigues, Mário S.
Pinho, Mariana G.
Cabrita, Eurico J.
Pereira, Manuela M.
author_role author
author2 Pires, Patrícia
Barreto, Andreia
Refojo, Patrícia N.
Silva, Micael S.
Fernandes, Pedro B.
Carapeto, Ana P.
Robalo, Tiago T.
Rodrigues, Mário S.
Pinho, Mariana G.
Cabrita, Eurico J.
Pereira, Manuela M.
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Tecnologia Química e Biológica António Xavier (ITQB)
UCIBIO - Applied Molecular Biosciences Unit
DQ - Departamento de Química
Faculdade de Ciências e Tecnologia (FCT)
RUN
dc.contributor.author.fl_str_mv Sousa, Filipe M.
Pires, Patrícia
Barreto, Andreia
Refojo, Patrícia N.
Silva, Micael S.
Fernandes, Pedro B.
Carapeto, Ana P.
Robalo, Tiago T.
Rodrigues, Mário S.
Pinho, Mariana G.
Cabrita, Eurico J.
Pereira, Manuela M.
dc.subject.por.fl_str_mv Bacterial respiration
DHODH
electron transfer
Flavoprotein
FMN
Quinone
Respiratory chain
Staphylococcus aureus
Biophysics
Biochemistry
Cell Biology
topic Bacterial respiration
DHODH
electron transfer
Flavoprotein
FMN
Quinone
Respiratory chain
Staphylococcus aureus
Biophysics
Biochemistry
Cell Biology
description Funding Information: Helena Gaspar is acknowledged for the HPLC analyses and Bruno Victor for advice on modelling. F.M.S. and M.S.S. are recipients of fellowships by Fundação para a Ciência e a Tecnologia (PD/BD/128213/2016 and PD/BD/128202/2016, respectively, both within the scope of the PhD program Molecular Biosciences PD/00133/2012). A.B. is recipient of a fellowship by Fundação para a Ciência e a Tecnologia UI/BD/153052/2022. The work was funded by Fundação para a Ciência e a Tecnologia ( PTDC/BIA-BQM/2599/2021 to M.M.P). The project was further supported by UIDB/04046/2020 and UIDP/04046/2020 Centre grants from FCT , Portugal (to BioISI), by LISBOA-01-0145-FEDER-007660 cofunded by FEDER through COMPETE2020-POCI and by Fundação para a Ciência e a Tecnologia and by UIDB/04612/2020 and UIDP/04612/2020 research unit grants from FCT (to Mostmicro). The NMR spectrometers are part of the National NMR Network (PTNMR) and are supported by Infrastructure Project N° 022161 (co-financed by FEDER through COMPETE 2020, POCI, and PORL and FCT through PIDDAC). Funding Information: Helena Gaspar is acknowledged for the HPLC analyses and Bruno Victor for advice on modelling. F.M.S. and M.S.S. are recipients of fellowships by Fundação para a Ciência e a Tecnologia (PD/BD/128213/2016 and PD/BD/128202/2016, respectively, both within the scope of the PhD program Molecular Biosciences PD/00133/2012). A.B. is recipient of a fellowship by Fundação para a Ciência e a Tecnologia UI/BD/153052/2022. The work was funded by Fundação para a Ciência e a Tecnologia (PTDC/BIA-BQM/2599/2021 to M.M.P). The project was further supported by UIDB/04046/2020 and UIDP/04046/2020 Centre grants from FCT, Portugal (to BioISI), by LISBOA-01-0145-FEDER-007660 cofunded by FEDER through COMPETE2020-POCI and by Fundação para a Ciência e a Tecnologia and by UIDB/04612/2020 and UIDP/04612/2020 research unit grants from FCT (to Mostmicro). The NMR spectrometers are part of the National NMR Network (PTNMR) and are supported by Infrastructure Project N° 022161 (co-financed by FEDER through COMPETE 2020, POCI, and PORL and FCT through PIDDAC). Publisher Copyright: © 2022 The Author(s)
publishDate 2023
dc.date.none.fl_str_mv 2023-10-03T22:19:19Z
2023-04-01
2023-04-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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url http://hdl.handle.net/10362/158656
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0005-2728
PURE: 72696123
https://doi.org/10.1016/j.bbabio.2022.148948
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eu_rights_str_mv openAccess
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