5GP1

Crystal structure of ZIKV NS5 Methyltransferase in complex with GTP and SAH

5GP1 の概要

• エントリーDOI: 10.2210/pdb5gp1/pdb
• 関連するPDBエントリー: 5GOZ
• 分子名称: RNA-directed RNA polymerase NS5, SULFATE ION, P1-7-METHYLGUANOSINE-P3-ADENOSINE-5',5'-TRIPHOSPHATE, ... (6 entities in total)
• 機能のキーワード: methyltransferase gtp complex, transferase
• 由来する生物種: Zika virus (ZIKV)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 93478.48

構造登録者

Zhang, C.,Jin, T. (登録日: 2016-07-30, 公開日: 2016-12-07, 最終更新日: 2025-09-17)

主引用文献

Zhang, C.,Feng, T.,Cheng, J.,Li, Y.,Yin, X.,Zeng, W.,Jin, X.,Li, Y.,Guo, F.,Jin, T.
Structure of the NS5 methyltransferase from Zika virus and implications in inhibitor design
Biochem. Biophys. Res. Commun., 492:624-630, 2017

PubMed Abstract: Recent outbreak of flavivirus Zika virus (ZIKV) in America has urged the basic as well as translational studies of this important human pathogen. The nonstructural protein 5 (NS5) of the flavivirus has an N-terminal methyltransferase (MTase) domain that plays critical roles in viral RNA genome capping. The null mutant of NS5 MTase is lethal for virus. Therefore, NS5 is a potential drug target for the treatment of Zika virus infection. In this study, we determined crystal structures of the ZIKV MTase in complex with GTP and RNA cap analogue GpppA. Structural analyses revealed highly conserved GTP/cap-binding pocket and S-adenosylmethionine (SAM)-binding pocket. Two conformations of the second base of the cap were identified, which suggests the flexibility of RNA conformation. In addition, the ligand-binding pockets identified a continuous region of hotspots suitable for drug design. Docking calculation shows that the Dengue virus inhibitor compound 10 may bind to the ZIKV MTase.

PubMed: 27866982
DOI: 10.1016/j.bbrc.2016.11.098

実験手法

X-RAY DIFFRACTION (2.444 Å)