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ツゲ ヒデアキ
TSUGE HIDEAKI
津下 英明 所属 京都産業大学 生命科学部 先端生命科学科 職種 教授 |
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| 言語種別 | 英語 |
| 発行・発表の年月 | 2013 |
| 形態種別 | 研究論文 |
| 査読 | 査読あり |
| 標題 | Conformational polymorphism of m7GTP in crystal structure of the PB2 middle domain from human influenza A virus. |
| 執筆形態 | その他 |
| 掲載誌名 | PLOS ONE |
| 出版社・発行元 | PUBLIC LIBRARY SCIENCE |
| 巻・号・頁 | 8(11) |
| 担当区分 | 最終著者,責任著者 |
| 著者・共著者 | Tsurumura T,Qiu H,Yoshida T,Tsumori Y,Hatakeyama D,Kuzuhara T,Tsuge H |
| 概要 | Influenza pandemics with human-to-human transmission of the virus are of great public concern, It is now recognized that a number of factors are necessary for human transmission and virulence, including several key mutations within the PI:32 subunit of RNA-dependent RNA polymerase, The structure of the middle domain in PB2 has been revealed with or without m(7)GTP, thus the middle domain is considered to be novel target for structure-based drug design. Here we report the crystal structure of the middle domain of H1N1 PB2 with or without m7GTP at 1.9 angstrom and 2.0 angstrom resolution, respectively, which has two mutations (P453H, I471T) to increase electrostatic potential and solubility. Here we report the m7GTP has unique conformation differ from the reported structure. 7-methyl-guanine is fixed in the pocket, but particularly significant change is seen in ribose and triphosphate region: the buried 7-methyl-guanine indeed binds in the pocket forming by H357, F404, E361 and K376 but the triphosphate continues directly to the outer domain. The presented conformation of m(7)GTP may be a clue for the anti-influenza drug-design. |
| DOI | 10.1371/journal.pone.0082020 |
| ISSN | 1932-6203 |
| PMID | 24312396 |
| Put Code(ORCID) | 11767703 |
| PermalinkURL | http://europepmc.org/abstract/med/24312396 |