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Protein oxidation mediated by heme-induced active site conversion specific for heme-regulated transcription factor, iron response regulator
This item is licensed under:Creative Commons Attribution 4.0 International
| Title: | Protein oxidation mediated by heme-induced active site conversion specific for heme-regulated transcription factor, iron response regulator |
| Authors: | Kitatsuji, Chihiro Browse this author | | Izumi, Kozue Browse this author | | Nambu, Shusuke Browse this author | | Kurogochi, Masaki Browse this author | | Uchida, Takeshi Browse this author | | Nishimura, Shin-Ichiro Browse this author | | Iwai, Kazuhiro Browse this author | | O'Brian, Mark R. Browse this author | | Ikeda-Saito, Masao Browse this author | | Ishimori, Koichiro Browse this author →KAKEN DB |
| Issue Date: | 5-Jan-2016 |
| Publisher: | Nature Publishing Group |
| Journal Title: | Scientific reports |
| Volume: | 6 |
| Start Page: | 18703 |
| Publisher DOI: | 10.1038/srep18703 |
| Abstract: | The Bradyrhizobium japonicum transcriptional regulator Irr (iron response regulator) is a key regulator of the iron homeostasis, which is degraded in response to heme binding via a mechanism that involves oxidative modification of the protein. Here, we show that heme-bound Irr activates O-2 to form highly reactive oxygen species (ROS) with the "active site conversion" from heme iron to non-heme iron to degrade itself. In the presence of heme and reductant, the ROS scavenging experiments show that Irr generates H2O2 from O-2 as found for other hemoproteins, but H2O2 is less effective in oxidizing the peptide, and further activation of H2O2 is suggested. Interestingly, we find a time-dependent decrease of the intensity of the Soret band and appearance of the characteristic EPR signal at g = 4.3 during the oxidation, showing the heme degradation and the successive formation of a non-heme iron site. Together with the mutational studies, we here propose a novel "two-step self-oxidative modification" mechanism, during which O-2 is activated to form H2O2 at the heme regulatory motif (HRM) site and the generated H2O2 is further converted into more reactive species such as OH at the non-heme iron site in the His-cluster region formed by the active site conversion. |
| Rights: | http://creativecommons.org/licenses/by/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/60742 |
| Appears in Collections: | 理学院・理学研究院 (Graduate School of Science / Faculty of Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 石森 浩一郎
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