Structural Characterization of Neisseria gonorrhoeae Bacterial Peroxidase—Insights into the Catalytic Cycle of Bacterial Peroxidases

Detalhes bibliográficos
Autor(a) principal: Nóbrega, Cláudia S.
Data de Publicação: 2023
Outros Autores: Carvalho, Ana Luísa, Romão, Maria João, Pauleta, Sofia R.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/151545
Resumo: Acknowledgments The authors would like to thank Lina Juknaité for her contribution in the initial crystallization studies. The authors acknowledge the European Synchrotron Radiation Facility and the Swiss Light Source for provision of synchrotron radiation facilities and access to beamlines BM30 and PXIII (X06DA), respectively.
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spelling Structural Characterization of Neisseria gonorrhoeae Bacterial Peroxidase—Insights into the Catalytic Cycle of Bacterial PeroxidasesBacterial peroxidasepathogenic bacteriaNeisseria gonorrhoeaeinhibitionAgricultural and Biological Sciences(all)SDG 3 - Good Health and Well-beingAcknowledgments The authors would like to thank Lina Juknaité for her contribution in the initial crystallization studies. The authors acknowledge the European Synchrotron Radiation Facility and the Swiss Light Source for provision of synchrotron radiation facilities and access to beamlines BM30 and PXIII (X06DA), respectively.Neisseria gonorrhoeae is an obligate human pathogenic bacterium responsible for gonorrhea, a sexually transmitted disease. The bacterial peroxidase, an enzyme present in the periplasm of this bacterium, detoxifies the cells against hydrogen peroxide and constitutes one of the primary defenses against exogenous and endogenous oxidative stress in this organism. The 38 kDa heterologously produced bacterial peroxidase was crystallized in the mixed-valence state, the active state, at pH 6.0, and the crystals were soaked with azide, producing the first azide-inhibited structure of this family of enzymes. The enzyme binds exogenous ligands such as cyanide and azide, which also inhibit the catalytic activity by coordinating the P heme iron, the active site, and competing with its substrate, hydrogen peroxide. The inhibition constants were estimated to be 0.4 ± 0.1 µM and 41 ± 5 mM for cyanide and azide, respectively. Imidazole also binds and inhibits the enzyme in a more complex mechanism by binding to P and E hemes, which changes the reduction potential of the latest heme. Based on the structures now reported, the catalytic cycle of bacterial peroxidases is revisited. The inhibition studies and the crystal structure of the inhibited enzyme comprise the first platform to search and develop inhibitors that target this enzyme as a possible new strategy against N. gonorrhoeae.UCIBIO - Applied Molecular Biosciences UnitDQ - Departamento de QuímicaRUNNóbrega, Cláudia S.Carvalho, Ana LuísaRomão, Maria JoãoPauleta, Sofia R.2023-04-03T22:15:23Z2023-03-262023-03-26T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article21application/pdfhttp://hdl.handle.net/10362/151545eng1422-0067PURE: 57231711https://doi.org/10.3390/ijms24076246info: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:RCAAP2024-05-22T18:10:46Zoai:run.unl.pt:10362/151545Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-05-22T18:10:46Repositório 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 Structural Characterization of Neisseria gonorrhoeae Bacterial Peroxidase—Insights into the Catalytic Cycle of Bacterial Peroxidases
title Structural Characterization of Neisseria gonorrhoeae Bacterial Peroxidase—Insights into the Catalytic Cycle of Bacterial Peroxidases
spellingShingle Structural Characterization of Neisseria gonorrhoeae Bacterial Peroxidase—Insights into the Catalytic Cycle of Bacterial Peroxidases
Nóbrega, Cláudia S.
Bacterial peroxidase
pathogenic bacteria
Neisseria gonorrhoeae
inhibition
Agricultural and Biological Sciences(all)
SDG 3 - Good Health and Well-being
title_short Structural Characterization of Neisseria gonorrhoeae Bacterial Peroxidase—Insights into the Catalytic Cycle of Bacterial Peroxidases
title_full Structural Characterization of Neisseria gonorrhoeae Bacterial Peroxidase—Insights into the Catalytic Cycle of Bacterial Peroxidases
title_fullStr Structural Characterization of Neisseria gonorrhoeae Bacterial Peroxidase—Insights into the Catalytic Cycle of Bacterial Peroxidases
title_full_unstemmed Structural Characterization of Neisseria gonorrhoeae Bacterial Peroxidase—Insights into the Catalytic Cycle of Bacterial Peroxidases
title_sort Structural Characterization of Neisseria gonorrhoeae Bacterial Peroxidase—Insights into the Catalytic Cycle of Bacterial Peroxidases
author Nóbrega, Cláudia S.
author_facet Nóbrega, Cláudia S.
Carvalho, Ana Luísa
Romão, Maria João
Pauleta, Sofia R.
author_role author
author2 Carvalho, Ana Luísa
Romão, Maria João
Pauleta, Sofia R.
author2_role author
author
author
dc.contributor.none.fl_str_mv UCIBIO - Applied Molecular Biosciences Unit
DQ - Departamento de Química
RUN
dc.contributor.author.fl_str_mv Nóbrega, Cláudia S.
Carvalho, Ana Luísa
Romão, Maria João
Pauleta, Sofia R.
dc.subject.por.fl_str_mv Bacterial peroxidase
pathogenic bacteria
Neisseria gonorrhoeae
inhibition
Agricultural and Biological Sciences(all)
SDG 3 - Good Health and Well-being
topic Bacterial peroxidase
pathogenic bacteria
Neisseria gonorrhoeae
inhibition
Agricultural and Biological Sciences(all)
SDG 3 - Good Health and Well-being
description Acknowledgments The authors would like to thank Lina Juknaité for her contribution in the initial crystallization studies. The authors acknowledge the European Synchrotron Radiation Facility and the Swiss Light Source for provision of synchrotron radiation facilities and access to beamlines BM30 and PXIII (X06DA), respectively.
publishDate 2023
dc.date.none.fl_str_mv 2023-04-03T22:15:23Z
2023-03-26
2023-03-26T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/151545
url http://hdl.handle.net/10362/151545
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1422-0067
PURE: 57231711
https://doi.org/10.3390/ijms24076246
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 21
application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv mluisa.alvim@gmail.com
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