Evidence for a ferryl intermediate in a heme-based dioxygenase

Autores
Lewis Ballester, Ariel; Batabyal, Dipanwita; Egawa, T.; Lu, Changyuan; Lin, Yu; Marti, Marcelo Adrian; Capece, Luciana; Estrin, Dario Ariel; Yeh, S. R.
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In contrast to the wide spectrum of cytochrome P450 monooxygenases, there are only 2 heme-based dioxygenases in humans: tryptophan dioxygenase (hTDO) and indoleamine 2,3-dioxygenase (hIDO). hTDO and hIDO catalyze the same oxidative ring cleavage reaction of L-tryptophan to N-formyl kynurenine, the initial and rate-limiting step of the kynurenine pathway. Despite immense interest, the mechanism by which the 2 enzymes execute the dioxygenase reaction remains elusive. Here, we report experimental evidence for a key ferryl intermediate of hIDO that supports a mechanism in which the 2 atoms of dioxygen are inserted into the substrate via a consecutive 2-step reaction. This finding introduces a paradigm shift in our understanding of the heme-based dioxygenase chemistry, which was previously believed to proceed via simultaneous incorporation of both atoms of dioxygen into the substrate. The ferryl intermediate is not observable during the hTDO reaction, highlighting the structural differences between the 2 dioxygenases, as well as the importance of stereoelectronic factors in modulating the reactions.
Fil: Ariel Lewis Ballester.
Fil: Dipanwita Batabyal.
Fil: Tsuyoshi Egawa.
Fil: Changyuan Lu.
Fil: Yu Lin.
Fil: Marti, Marcelo Adrian.
Fil: Capece, Luciana.
Fil: Estrin, Dario Ariel.
Fil: Syun-Ru Yeh.
Materia
Indoleamine 2,3-Dioxygenase
Qm-Mm
Resonance Raman Spectroscopy
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/104129
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/104129
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Evidence for a ferryl intermediate in a heme-based dioxygenaseLewis Ballester, ArielBatabyal, DipanwitaEgawa, T.Lu, ChangyuanLin, YuMarti, Marcelo AdrianCapece, LucianaEstrin, Dario ArielYeh, S. R.Indoleamine 2,3-DioxygenaseQm-MmResonance Raman Spectroscopyhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1In contrast to the wide spectrum of cytochrome P450 monooxygenases, there are only 2 heme-based dioxygenases in humans: tryptophan dioxygenase (hTDO) and indoleamine 2,3-dioxygenase (hIDO). hTDO and hIDO catalyze the same oxidative ring cleavage reaction of L-tryptophan to N-formyl kynurenine, the initial and rate-limiting step of the kynurenine pathway. Despite immense interest, the mechanism by which the 2 enzymes execute the dioxygenase reaction remains elusive. Here, we report experimental evidence for a key ferryl intermediate of hIDO that supports a mechanism in which the 2 atoms of dioxygen are inserted into the substrate via a consecutive 2-step reaction. This finding introduces a paradigm shift in our understanding of the heme-based dioxygenase chemistry, which was previously believed to proceed via simultaneous incorporation of both atoms of dioxygen into the substrate. The ferryl intermediate is not observable during the hTDO reaction, highlighting the structural differences between the 2 dioxygenases, as well as the importance of stereoelectronic factors in modulating the reactions.Fil: Ariel Lewis Ballester.Fil: Dipanwita Batabyal.Fil: Tsuyoshi Egawa.Fil: Changyuan Lu.Fil: Yu Lin.Fil: Marti, Marcelo Adrian.Fil: Capece, Luciana.Fil: Estrin, Dario Ariel.Fil: Syun-Ru Yeh.National Academy of Sciences2009-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/104129Lewis Ballester, Ariel; Batabyal, Dipanwita; Egawa, T.; Lu, Changyuan; Lin, Yu; et al.; Evidence for a ferryl intermediate in a heme-based dioxygenase; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 106; 41; 9-2009; 17371-173760027-8424CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.pnas.org/content/106/41/17371info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.0906655106info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:36:58Zoai:ri.conicet.gov.ar:11336/104129instacron: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 10:36:58.479CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Evidence for a ferryl intermediate in a heme-based dioxygenase
title Evidence for a ferryl intermediate in a heme-based dioxygenase
spellingShingle Evidence for a ferryl intermediate in a heme-based dioxygenase
Lewis Ballester, Ariel
Indoleamine 2,3-Dioxygenase
Qm-Mm
Resonance Raman Spectroscopy
title_short Evidence for a ferryl intermediate in a heme-based dioxygenase
title_full Evidence for a ferryl intermediate in a heme-based dioxygenase
title_fullStr Evidence for a ferryl intermediate in a heme-based dioxygenase
title_full_unstemmed Evidence for a ferryl intermediate in a heme-based dioxygenase
title_sort Evidence for a ferryl intermediate in a heme-based dioxygenase
dc.creator.none.fl_str_mv Lewis Ballester, Ariel
Batabyal, Dipanwita
Egawa, T.
Lu, Changyuan
Lin, Yu
Marti, Marcelo Adrian
Capece, Luciana
Estrin, Dario Ariel
Yeh, S. R.
author Lewis Ballester, Ariel
author_facet Lewis Ballester, Ariel
Batabyal, Dipanwita
Egawa, T.
Lu, Changyuan
Lin, Yu
Marti, Marcelo Adrian
Capece, Luciana
Estrin, Dario Ariel
Yeh, S. R.
author_role author
author2 Batabyal, Dipanwita
Egawa, T.
Lu, Changyuan
Lin, Yu
Marti, Marcelo Adrian
Capece, Luciana
Estrin, Dario Ariel
Yeh, S. R.
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Indoleamine 2,3-Dioxygenase
Qm-Mm
Resonance Raman Spectroscopy
topic Indoleamine 2,3-Dioxygenase
Qm-Mm
Resonance Raman Spectroscopy
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv In contrast to the wide spectrum of cytochrome P450 monooxygenases, there are only 2 heme-based dioxygenases in humans: tryptophan dioxygenase (hTDO) and indoleamine 2,3-dioxygenase (hIDO). hTDO and hIDO catalyze the same oxidative ring cleavage reaction of L-tryptophan to N-formyl kynurenine, the initial and rate-limiting step of the kynurenine pathway. Despite immense interest, the mechanism by which the 2 enzymes execute the dioxygenase reaction remains elusive. Here, we report experimental evidence for a key ferryl intermediate of hIDO that supports a mechanism in which the 2 atoms of dioxygen are inserted into the substrate via a consecutive 2-step reaction. This finding introduces a paradigm shift in our understanding of the heme-based dioxygenase chemistry, which was previously believed to proceed via simultaneous incorporation of both atoms of dioxygen into the substrate. The ferryl intermediate is not observable during the hTDO reaction, highlighting the structural differences between the 2 dioxygenases, as well as the importance of stereoelectronic factors in modulating the reactions.
Fil: Ariel Lewis Ballester.
Fil: Dipanwita Batabyal.
Fil: Tsuyoshi Egawa.
Fil: Changyuan Lu.
Fil: Yu Lin.
Fil: Marti, Marcelo Adrian.
Fil: Capece, Luciana.
Fil: Estrin, Dario Ariel.
Fil: Syun-Ru Yeh.
description In contrast to the wide spectrum of cytochrome P450 monooxygenases, there are only 2 heme-based dioxygenases in humans: tryptophan dioxygenase (hTDO) and indoleamine 2,3-dioxygenase (hIDO). hTDO and hIDO catalyze the same oxidative ring cleavage reaction of L-tryptophan to N-formyl kynurenine, the initial and rate-limiting step of the kynurenine pathway. Despite immense interest, the mechanism by which the 2 enzymes execute the dioxygenase reaction remains elusive. Here, we report experimental evidence for a key ferryl intermediate of hIDO that supports a mechanism in which the 2 atoms of dioxygen are inserted into the substrate via a consecutive 2-step reaction. This finding introduces a paradigm shift in our understanding of the heme-based dioxygenase chemistry, which was previously believed to proceed via simultaneous incorporation of both atoms of dioxygen into the substrate. The ferryl intermediate is not observable during the hTDO reaction, highlighting the structural differences between the 2 dioxygenases, as well as the importance of stereoelectronic factors in modulating the reactions.
publishDate 2009
dc.date.none.fl_str_mv 2009-09
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/11336/104129
Lewis Ballester, Ariel; Batabyal, Dipanwita; Egawa, T.; Lu, Changyuan; Lin, Yu; et al.; Evidence for a ferryl intermediate in a heme-based dioxygenase; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 106; 41; 9-2009; 17371-17376
0027-8424
CONICET Digital
CONICET
url http://hdl.handle.net/11336/104129
identifier_str_mv Lewis Ballester, Ariel; Batabyal, Dipanwita; Egawa, T.; Lu, Changyuan; Lin, Yu; et al.; Evidence for a ferryl intermediate in a heme-based dioxygenase; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 106; 41; 9-2009; 17371-17376
0027-8424
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.pnas.org/content/106/41/17371
info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.0906655106
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
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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