Crystal Structure of the Peroxo-diiron(III) Intermediate of Deoxyhypusine Hydroxylase, an Oxygenase Involved in Hypusination

Autores
Han, Zhenggang; Sakai, Naoki; Boettger, Lars; Klinke, Sebastian; Hauber, Joachim; Trautwein; Alfred; Hilgenfeld, Rolf
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Deoxyhypusine hydroxylase (DOHH) is a non-heme diiron enzyme involved in the posttranslational modification of a critical lysine residue of eukaryotic translation initiation factor 5A (eIF-5A) to yield the unusual amino acid residue hypusine. This modification is essential for the role of eIF-5A in translation and in nuclear export of a group of specific mRNAs. The diiron center of human DOHH (hDOHH) forms a peroxo-diiron(III) intermediate (hDOHHperoxo) when its reduced form reacts with O2. hDOHHperoxo has a lifetime exceeding that of the peroxo intermediates of other diiron enzymes by several orders of magnitude. Here we report the 1.7-Å crystal structures of hDOHHperoxo and a complex with glycerol. The structure of hDOHHperoxo reveals the presence of a μ-1,2-peroxo-diiron(III) species at the active site. Augmented by UV/Vis and Mössbauer spectroscopic studies, the crystal structures offer explanations for the extreme longevity of hDOHHperoxo and illustrate how the enzyme specifically recognizes its only substrate, deoxyhypusine-eIF-5A.
Fil: Han, Zhenggang. University of Lübeck; Alemania
Fil: Sakai, Naoki. University of Lübeck; Alemania
Fil: Boettger, Lars. University of Lübeck; Alemania
Fil: Klinke, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina. University of Lübeck; Alemania
Fil: Hauber, Joachim. Leibniz Institute for Experimental Virology; Alemania
Fil: Trautwein; Alfred. University of Lübeck; Alemania
Fil: Hilgenfeld, Rolf. University of Lübeck; Alemania
Materia
Deoxyhypusine Hydroxylase
Structure
Hypusination
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/10496
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/10496
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Crystal Structure of the Peroxo-diiron(III) Intermediate of Deoxyhypusine Hydroxylase, an Oxygenase Involved in HypusinationHan, ZhenggangSakai, NaokiBoettger, LarsKlinke, SebastianHauber, JoachimTrautwein; AlfredHilgenfeld, RolfDeoxyhypusine HydroxylaseStructureHypusinationhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Deoxyhypusine hydroxylase (DOHH) is a non-heme diiron enzyme involved in the posttranslational modification of a critical lysine residue of eukaryotic translation initiation factor 5A (eIF-5A) to yield the unusual amino acid residue hypusine. This modification is essential for the role of eIF-5A in translation and in nuclear export of a group of specific mRNAs. The diiron center of human DOHH (hDOHH) forms a peroxo-diiron(III) intermediate (hDOHHperoxo) when its reduced form reacts with O2. hDOHHperoxo has a lifetime exceeding that of the peroxo intermediates of other diiron enzymes by several orders of magnitude. Here we report the 1.7-Å crystal structures of hDOHHperoxo and a complex with glycerol. The structure of hDOHHperoxo reveals the presence of a μ-1,2-peroxo-diiron(III) species at the active site. Augmented by UV/Vis and Mössbauer spectroscopic studies, the crystal structures offer explanations for the extreme longevity of hDOHHperoxo and illustrate how the enzyme specifically recognizes its only substrate, deoxyhypusine-eIF-5A.Fil: Han, Zhenggang. University of Lübeck; AlemaniaFil: Sakai, Naoki. University of Lübeck; AlemaniaFil: Boettger, Lars. University of Lübeck; AlemaniaFil: Klinke, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina. University of Lübeck; AlemaniaFil: Hauber, Joachim. Leibniz Institute for Experimental Virology; AlemaniaFil: Trautwein; Alfred. University of Lübeck; AlemaniaFil: Hilgenfeld, Rolf. University of Lübeck; AlemaniaCell Press2015-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/10496Han, Zhenggang; Sakai, Naoki; Boettger, Lars; Klinke, Sebastian; Hauber, Joachim; et al.; Crystal Structure of the Peroxo-diiron(III) Intermediate of Deoxyhypusine Hydroxylase, an Oxygenase Involved in Hypusination; Cell Press; Structure With Folding & Design.; 23; 5; 5-2015; 882-8920969-2126enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0969212615000805info:eu-repo/semantics/altIdentifier/doi/10.1016/j.str.2015.03.002info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:47:13Zoai:ri.conicet.gov.ar:11336/10496instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:47:13.609CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Crystal Structure of the Peroxo-diiron(III) Intermediate of Deoxyhypusine Hydroxylase, an Oxygenase Involved in Hypusination
title Crystal Structure of the Peroxo-diiron(III) Intermediate of Deoxyhypusine Hydroxylase, an Oxygenase Involved in Hypusination
spellingShingle Crystal Structure of the Peroxo-diiron(III) Intermediate of Deoxyhypusine Hydroxylase, an Oxygenase Involved in Hypusination
Han, Zhenggang
Deoxyhypusine Hydroxylase
Structure
Hypusination
title_short Crystal Structure of the Peroxo-diiron(III) Intermediate of Deoxyhypusine Hydroxylase, an Oxygenase Involved in Hypusination
title_full Crystal Structure of the Peroxo-diiron(III) Intermediate of Deoxyhypusine Hydroxylase, an Oxygenase Involved in Hypusination
title_fullStr Crystal Structure of the Peroxo-diiron(III) Intermediate of Deoxyhypusine Hydroxylase, an Oxygenase Involved in Hypusination
title_full_unstemmed Crystal Structure of the Peroxo-diiron(III) Intermediate of Deoxyhypusine Hydroxylase, an Oxygenase Involved in Hypusination
title_sort Crystal Structure of the Peroxo-diiron(III) Intermediate of Deoxyhypusine Hydroxylase, an Oxygenase Involved in Hypusination
dc.creator.none.fl_str_mv Han, Zhenggang
Sakai, Naoki
Boettger, Lars
Klinke, Sebastian
Hauber, Joachim
Trautwein; Alfred
Hilgenfeld, Rolf
author Han, Zhenggang
author_facet Han, Zhenggang
Sakai, Naoki
Boettger, Lars
Klinke, Sebastian
Hauber, Joachim
Trautwein; Alfred
Hilgenfeld, Rolf
author_role author
author2 Sakai, Naoki
Boettger, Lars
Klinke, Sebastian
Hauber, Joachim
Trautwein; Alfred
Hilgenfeld, Rolf
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Deoxyhypusine Hydroxylase
Structure
Hypusination
topic Deoxyhypusine Hydroxylase
Structure
Hypusination
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Deoxyhypusine hydroxylase (DOHH) is a non-heme diiron enzyme involved in the posttranslational modification of a critical lysine residue of eukaryotic translation initiation factor 5A (eIF-5A) to yield the unusual amino acid residue hypusine. This modification is essential for the role of eIF-5A in translation and in nuclear export of a group of specific mRNAs. The diiron center of human DOHH (hDOHH) forms a peroxo-diiron(III) intermediate (hDOHHperoxo) when its reduced form reacts with O2. hDOHHperoxo has a lifetime exceeding that of the peroxo intermediates of other diiron enzymes by several orders of magnitude. Here we report the 1.7-Å crystal structures of hDOHHperoxo and a complex with glycerol. The structure of hDOHHperoxo reveals the presence of a μ-1,2-peroxo-diiron(III) species at the active site. Augmented by UV/Vis and Mössbauer spectroscopic studies, the crystal structures offer explanations for the extreme longevity of hDOHHperoxo and illustrate how the enzyme specifically recognizes its only substrate, deoxyhypusine-eIF-5A.
Fil: Han, Zhenggang. University of Lübeck; Alemania
Fil: Sakai, Naoki. University of Lübeck; Alemania
Fil: Boettger, Lars. University of Lübeck; Alemania
Fil: Klinke, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina. University of Lübeck; Alemania
Fil: Hauber, Joachim. Leibniz Institute for Experimental Virology; Alemania
Fil: Trautwein; Alfred. University of Lübeck; Alemania
Fil: Hilgenfeld, Rolf. University of Lübeck; Alemania
description Deoxyhypusine hydroxylase (DOHH) is a non-heme diiron enzyme involved in the posttranslational modification of a critical lysine residue of eukaryotic translation initiation factor 5A (eIF-5A) to yield the unusual amino acid residue hypusine. This modification is essential for the role of eIF-5A in translation and in nuclear export of a group of specific mRNAs. The diiron center of human DOHH (hDOHH) forms a peroxo-diiron(III) intermediate (hDOHHperoxo) when its reduced form reacts with O2. hDOHHperoxo has a lifetime exceeding that of the peroxo intermediates of other diiron enzymes by several orders of magnitude. Here we report the 1.7-Å crystal structures of hDOHHperoxo and a complex with glycerol. The structure of hDOHHperoxo reveals the presence of a μ-1,2-peroxo-diiron(III) species at the active site. Augmented by UV/Vis and Mössbauer spectroscopic studies, the crystal structures offer explanations for the extreme longevity of hDOHHperoxo and illustrate how the enzyme specifically recognizes its only substrate, deoxyhypusine-eIF-5A.
publishDate 2015
dc.date.none.fl_str_mv 2015-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/10496
Han, Zhenggang; Sakai, Naoki; Boettger, Lars; Klinke, Sebastian; Hauber, Joachim; et al.; Crystal Structure of the Peroxo-diiron(III) Intermediate of Deoxyhypusine Hydroxylase, an Oxygenase Involved in Hypusination; Cell Press; Structure With Folding & Design.; 23; 5; 5-2015; 882-892
0969-2126
url http://hdl.handle.net/11336/10496
identifier_str_mv Han, Zhenggang; Sakai, Naoki; Boettger, Lars; Klinke, Sebastian; Hauber, Joachim; et al.; Crystal Structure of the Peroxo-diiron(III) Intermediate of Deoxyhypusine Hydroxylase, an Oxygenase Involved in Hypusination; Cell Press; Structure With Folding & Design.; 23; 5; 5-2015; 882-892
0969-2126
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0969212615000805
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.str.2015.03.002
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Cell Press
publisher.none.fl_str_mv Cell Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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