5YJW
Structure of the Ndi1 protein from Saccharomyces cerevisiae in complex with the competitive inhibitor, stigmatellin.
Summary for 5YJW
| Entry DOI | 10.2210/pdb5yjw/pdb |
| Descriptor | Rotenone-insensitive NADH-ubiquinone oxidoreductase, mitochondrial, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, STIGMATELLIN A, ... (12 entities in total) |
| Functional Keywords | monotopic membrane protein, nucleotide-binding domain, oxidoreductase |
| Biological source | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) |
| Cellular location | Mitochondrion inner membrane ; Peripheral membrane protein ; Matrix side : P32340 |
| Total number of polymer chains | 1 |
| Total formula weight | 58819.22 |
| Authors | Yamasita, T.,Inaoka, D.K.,Shiba, T.,Oohashi, T.,Iwata, S.,Yagi, T.,Kosaka, H.,Harada, S.,Kita, K.,Hirano, K. (deposition date: 2017-10-11, release date: 2018-02-14, Last modification date: 2023-11-22) |
| Primary citation | Yamashita, T.,Inaoka, D.K.,Shiba, T.,Oohashi, T.,Iwata, S.,Yagi, T.,Kosaka, H.,Miyoshi, H.,Harada, S.,Kita, K.,Hirano, K. Ubiquinone binding site of yeast NADH dehydrogenase revealed by structures binding novel competitive- and mixed-type inhibitors Sci Rep, 8:2427-2427, 2018 Cited by PubMed 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. PubMed: 29402945DOI: 10.1038/s41598-018-20775-6 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.85 Å) |
Structure validation
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