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A substrate-bound structure of cyanobacterial biliverdin reductase identifies stacked substrates as critical for activity
Biliverdin reductase catalyses the last step in haem degradation and produces the major lipophilic antioxidant bilirubin via reduction of biliverdin, using NAD(P)H as a cofactor. Despite the importance of biliverdin reductase in maintaining the redox balance, the molecular details of the reaction it...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5309722/ https://www.ncbi.nlm.nih.gov/pubmed/28169272 http://dx.doi.org/10.1038/ncomms14397 |
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author | Takao, Haruna Hirabayashi, Kei Nishigaya, Yuki Kouriki, Haruna Nakaniwa, Tetsuko Hagiwara, Yoshinori Harada, Jiro Sato, Hideaki Yamazaki, Toshimasa Sakakibara, Yoichi Suiko, Masahito Asada, Yujiro Takahashi, Yasuhiro Yamamoto, Ken Fukuyama, Keiichi Sugishima, Masakazu Wada, Kei |
author_facet | Takao, Haruna Hirabayashi, Kei Nishigaya, Yuki Kouriki, Haruna Nakaniwa, Tetsuko Hagiwara, Yoshinori Harada, Jiro Sato, Hideaki Yamazaki, Toshimasa Sakakibara, Yoichi Suiko, Masahito Asada, Yujiro Takahashi, Yasuhiro Yamamoto, Ken Fukuyama, Keiichi Sugishima, Masakazu Wada, Kei |
author_sort | Takao, Haruna |
collection | PubMed |
description | Biliverdin reductase catalyses the last step in haem degradation and produces the major lipophilic antioxidant bilirubin via reduction of biliverdin, using NAD(P)H as a cofactor. Despite the importance of biliverdin reductase in maintaining the redox balance, the molecular details of the reaction it catalyses remain unknown. Here we present the crystal structure of biliverdin reductase in complex with biliverdin and NADP(+). Unexpectedly, two biliverdin molecules, which we designated the proximal and distal biliverdins, bind with stacked geometry in the active site. The nicotinamide ring of the NADP(+) is located close to the reaction site on the proximal biliverdin, supporting that the hydride directly attacks this position of the proximal biliverdin. The results of mutagenesis studies suggest that a conserved Arg185 is essential for the catalysis. The distal biliverdin probably acts as a conduit to deliver the proton from Arg185 to the proximal biliverdin, thus yielding bilirubin. |
format | Online Article Text |
id | pubmed-5309722 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53097222017-02-27 A substrate-bound structure of cyanobacterial biliverdin reductase identifies stacked substrates as critical for activity Takao, Haruna Hirabayashi, Kei Nishigaya, Yuki Kouriki, Haruna Nakaniwa, Tetsuko Hagiwara, Yoshinori Harada, Jiro Sato, Hideaki Yamazaki, Toshimasa Sakakibara, Yoichi Suiko, Masahito Asada, Yujiro Takahashi, Yasuhiro Yamamoto, Ken Fukuyama, Keiichi Sugishima, Masakazu Wada, Kei Nat Commun Article Biliverdin reductase catalyses the last step in haem degradation and produces the major lipophilic antioxidant bilirubin via reduction of biliverdin, using NAD(P)H as a cofactor. Despite the importance of biliverdin reductase in maintaining the redox balance, the molecular details of the reaction it catalyses remain unknown. Here we present the crystal structure of biliverdin reductase in complex with biliverdin and NADP(+). Unexpectedly, two biliverdin molecules, which we designated the proximal and distal biliverdins, bind with stacked geometry in the active site. The nicotinamide ring of the NADP(+) is located close to the reaction site on the proximal biliverdin, supporting that the hydride directly attacks this position of the proximal biliverdin. The results of mutagenesis studies suggest that a conserved Arg185 is essential for the catalysis. The distal biliverdin probably acts as a conduit to deliver the proton from Arg185 to the proximal biliverdin, thus yielding bilirubin. Nature Publishing Group 2017-02-07 /pmc/articles/PMC5309722/ /pubmed/28169272 http://dx.doi.org/10.1038/ncomms14397 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Takao, Haruna Hirabayashi, Kei Nishigaya, Yuki Kouriki, Haruna Nakaniwa, Tetsuko Hagiwara, Yoshinori Harada, Jiro Sato, Hideaki Yamazaki, Toshimasa Sakakibara, Yoichi Suiko, Masahito Asada, Yujiro Takahashi, Yasuhiro Yamamoto, Ken Fukuyama, Keiichi Sugishima, Masakazu Wada, Kei A substrate-bound structure of cyanobacterial biliverdin reductase identifies stacked substrates as critical for activity |
title | A substrate-bound structure of cyanobacterial biliverdin reductase identifies stacked substrates as critical for activity |
title_full | A substrate-bound structure of cyanobacterial biliverdin reductase identifies stacked substrates as critical for activity |
title_fullStr | A substrate-bound structure of cyanobacterial biliverdin reductase identifies stacked substrates as critical for activity |
title_full_unstemmed | A substrate-bound structure of cyanobacterial biliverdin reductase identifies stacked substrates as critical for activity |
title_short | A substrate-bound structure of cyanobacterial biliverdin reductase identifies stacked substrates as critical for activity |
title_sort | substrate-bound structure of cyanobacterial biliverdin reductase identifies stacked substrates as critical for activity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5309722/ https://www.ncbi.nlm.nih.gov/pubmed/28169272 http://dx.doi.org/10.1038/ncomms14397 |
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