Access count of this item: 50

Files in This Item:
File Description SizeFormat 
s41598-018-20775-6.pdf3.57 MBAdobe PDFView/Open
Title: Ubiquinone binding site of yeast NADH dehydrogenase revealed by structures binding novel competitive- and mixed-type inhibitors
Authors: Yamashita, Tetsuo
Inaoka, Daniel Ken
Shiba, Tomoo
Oohashi, Takumi
Iwata, So  kyouindb  KAKEN_id
Yagi, Takao
Kosaka, Hiroaki
Miyoshi, Hideto  kyouindb  KAKEN_id
Harada, Shigeharu
Kita, Kiyoshi
Hirano, Katsuya
Author's alias: 三芳, 秀人
岩田, 想
Issue Date: 5-Feb-2018
Publisher: Springer Nature
Journal title: Scientific reports
Volume: 8
Thesis number: 2427
Abstract: Yeast Ndi1 is a monotopic alternative NADH dehydrogenase. Its crystal structure in complex with the electron acceptor, ubiquinone, has been determined. However, there has been controversy regarding the ubiquinone binding site. To address these points, we identified the first competitive inhibitor of Ndi1, stigmatellin, along with new mixed-type inhibitors, AC0-12 and myxothiazol, and thereby determined the crystal structures of Ndi1 in complexes with the inhibitors. Two separate binding sites of stigmatellin, STG-1 and STG-2, were observed. The electron density at STG-1, located at the vicinity of the FAD cofactor, further demonstrated two binding modes: STG-1a and STG-1b. AC0-12 and myxothiazol are also located at the vicinity of FAD. The comparison of the binding modes among stigmatellin at STG-1, AC0-12, and myxothiazol revealed a unique position for the aliphatic tail of stigmatellin at STG-1a. Mutations of amino acid residues that interact with this aliphatic tail at STG-1a reduced the affinity of Ndi1 for ubiquinone. In conclusion, the position of the aliphatic tail of stigmatellin at STG-1a provides a structural basis for its competitive inhibition of Ndi1. The inherent binding site of ubiquinone is suggested to overlap with STG-1a that is distinct from the binding site for NADH.
Rights: © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
URI: http://hdl.handle.net/2433/234721
DOI(Published Version): 10.1038/s41598-018-20775-6
PubMed ID: 29402945
Appears in Collections:Journal Articles

Show full item record

Export to RefWorks


Export Format: 


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.