New Insights into Hemopexin-Binding to Hemin and Hemoglobin

Bibliographic Details
Main Author: Lechuga, Guilherme C.
Publication Date: 2022
Other Authors: Napoleão-Pêgo, Paloma, Morel, Carlos M., Provance, David W., De-Simone, Salvatore G.
Format: Article
Language: eng
Source: Repositório Institucional da FIOCRUZ (ARCA)
Download full: https://www.arca.fiocruz.br/handle/icict/52505
Summary: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia Para Inovação em Doenças da População Negligenciadas. Rio de Janeiro, RJ, Brasil.
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spelling Lechuga, Guilherme C.Napoleão-Pêgo, PalomaMorel, Carlos M.Provance, David W.De-Simone, Salvatore G.2022-05-02T18:58:56Z2022-05-02T18:58:56Z2022LECHUGA, Guilherme C. et al. New Insights into Hemopexin-Binding to Hemin and Hemoglobin. International Journal of Molecular Sciences, v. v. 23, n. 3789, p. 1 - 11, Mar. 2022.1422-0067https://www.arca.fiocruz.br/handle/icict/5250510.3390/ ijms23073789engMDPIHemopexinaHemoglobinaLigação proteína-proteínaHeminaHemopexinHemoglobinProtein-protein bindingHeminNew Insights into Hemopexin-Binding to Hemin and Hemoglobininfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia Para Inovação em Doenças da População Negligenciadas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia Para Inovação em Doenças da População Negligenciadas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil .Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia Para Inovação em Doenças da População Negligenciadas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia Para Inovação em Doenças da População Negligenciadas. Rio de Janeiro, RJ, Brasil / Universidade Federal Fluminense. Instituto de Biologia. Departametno de Biologia Celular e Molecular. Niterói, RJ, BrasilHemopexin (Hx) is a plasma glycoprotein that scavenges heme (Fe(III) protoporphyrin IX). Hx has important implications in hemolytic disorders and hemorrhagic conditions because releasing hemoglobin increases the labile heme, which is potentially toxic, thus producing oxidative stress. Therefore, Hx has been considered for therapeutic use and diagnostics. In this work, we analyzed and mapped the interaction sequences of Hx with hemin and hemoglobin. The spot-synthesis technique was used to map human hemopexin (P02790) binding to hemin and human hemoglobin. A library of 15 amino acid peptides with a 10-amino acid overlap was designed to represent the entire coding region (aa 1-462) of hemopexin and synthesized onto cellulose membranes. An in silico approach was taken to analyze the amino acid frequency in the identified interaction regions, and molecular docking was applied to assess the protein-protein interaction. Seven linear peptide sequences in Hx were identified to bind hemin (H1–H7), and five were described for Hb (Hb1–Hb5) interaction, with just two sequences shared between hemin and Hb. The amino acid composition of the identified sequences demonstrated that histidine residues are relevant for heme binding. H105, H293, H373, H400, H429, and H462 were distributed in the H1–H7 peptide sequences, but other residues may also play an important role. Molecular docking analysis demonstrated Hx’s association with the -chain of Hb, with several hotspot amino acids that coordinated the interaction. This study provides new insights into Hx-hemin binding motifs and protein-protein interactions with Hb. The identified binding sequences and specific peptides can be used for therapeutic purposes and diagnostics as hemopexin is under investigation to treat different diseases and there is an urgent need for diagnostics using labile heme when monitoring hemolysis.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/52505/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALGuilhermeLechuga_SalvatoredeSimone_etal_IOC_2022.pdfGuilhermeLechuga_SalvatoredeSimone_etal_IOC_2022.pdfapplication/pdf2138819https://www.arca.fiocruz.br/bitstream/icict/52505/2/GuilhermeLechuga_SalvatoredeSimone_etal_IOC_2022.pdf0f84ba078296d4c9171c6d8d57f8efe6MD52icict/525052022-05-02 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dc.title.pt_BR.fl_str_mv New Insights into Hemopexin-Binding to Hemin and Hemoglobin
title New Insights into Hemopexin-Binding to Hemin and Hemoglobin
spellingShingle New Insights into Hemopexin-Binding to Hemin and Hemoglobin
Lechuga, Guilherme C.
Hemopexina
Hemoglobina
Ligação proteína-proteína
Hemina
Hemopexin
Hemoglobin
Protein-protein binding
Hemin
title_short New Insights into Hemopexin-Binding to Hemin and Hemoglobin
title_full New Insights into Hemopexin-Binding to Hemin and Hemoglobin
title_fullStr New Insights into Hemopexin-Binding to Hemin and Hemoglobin
title_full_unstemmed New Insights into Hemopexin-Binding to Hemin and Hemoglobin
title_sort New Insights into Hemopexin-Binding to Hemin and Hemoglobin
author Lechuga, Guilherme C.
author_facet Lechuga, Guilherme C.
Napoleão-Pêgo, Paloma
Morel, Carlos M.
Provance, David W.
De-Simone, Salvatore G.
author_role author
author2 Napoleão-Pêgo, Paloma
Morel, Carlos M.
Provance, David W.
De-Simone, Salvatore G.
author2_role author
author
author
author
dc.contributor.author.fl_str_mv Lechuga, Guilherme C.
Napoleão-Pêgo, Paloma
Morel, Carlos M.
Provance, David W.
De-Simone, Salvatore G.
dc.subject.other.pt_BR.fl_str_mv Hemopexina
Hemoglobina
Ligação proteína-proteína
Hemina
topic Hemopexina
Hemoglobina
Ligação proteína-proteína
Hemina
Hemopexin
Hemoglobin
Protein-protein binding
Hemin
dc.subject.en.pt_BR.fl_str_mv Hemopexin
Hemoglobin
Protein-protein binding
Hemin
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia Para Inovação em Doenças da População Negligenciadas. Rio de Janeiro, RJ, Brasil.
publishDate 2022
dc.date.accessioned.fl_str_mv 2022-05-02T18:58:56Z
dc.date.available.fl_str_mv 2022-05-02T18:58:56Z
dc.date.issued.fl_str_mv 2022
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.citation.fl_str_mv LECHUGA, Guilherme C. et al. New Insights into Hemopexin-Binding to Hemin and Hemoglobin. International Journal of Molecular Sciences, v. v. 23, n. 3789, p. 1 - 11, Mar. 2022.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/52505
dc.identifier.issn.pt_BR.fl_str_mv 1422-0067
dc.identifier.doi.none.fl_str_mv 10.3390/ ijms23073789
identifier_str_mv LECHUGA, Guilherme C. et al. New Insights into Hemopexin-Binding to Hemin and Hemoglobin. International Journal of Molecular Sciences, v. v. 23, n. 3789, p. 1 - 11, Mar. 2022.
1422-0067
10.3390/ ijms23073789
url https://www.arca.fiocruz.br/handle/icict/52505
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/52505/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/52505/2/GuilhermeLechuga_SalvatoredeSimone_etal_IOC_2022.pdf
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bitstream.checksumAlgorithm.fl_str_mv MD5
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repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv repositorio.arca@fiocruz.br
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