6WKS

Structure of SARS-CoV-2 nsp16/nsp10 in complex with RNA cap analogue (m7GpppA) and S-adenosylmethionine

これはPDB形式変換不可エントリーです。

6WKS の概要

• エントリーDOI: 10.2210/pdb6wks/pdb
• 分子名称: 2'-O-methyltransferase, Non-structural protein 10, S-ADENOSYLMETHIONINE, ... (8 entities in total)
• 機能のキーワード: enzyme, transferase, hydrolase, protein assembly, rna binding protein, methyltransferase
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 49804.18

構造登録者

Gupta, Y.K.,Viswanathan, T.,Arya, S.,Qi, S.,Misra, A.,Chan, S.-H. (登録日: 2020-04-16, 公開日: 2020-05-06, 最終更新日: 2023-10-18)

主引用文献

Viswanathan, T.,Arya, S.,Chan, S.H.,Qi, S.,Dai, N.,Misra, A.,Park, J.G.,Oladunni, F.,Kovalskyy, D.,Hromas, R.A.,Martinez-Sobrido, L.,Gupta, Y.K.
Structural basis of RNA cap modification by SARS-CoV-2.
Nat Commun, 11:3718-3718, 2020

PubMed Abstract: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19 illness, has caused millions of infections worldwide. In SARS coronaviruses, the non-structural protein 16 (nsp16), in conjunction with nsp10, methylates the 5'-end of virally encoded mRNAs to mimic cellular mRNAs, thus protecting the virus from host innate immune restriction. We report here the high-resolution structure of a ternary complex of SARS-CoV-2 nsp16 and nsp10 in the presence of cognate RNA substrate analogue and methyl donor, S-adenosyl methionine (SAM). The nsp16/nsp10 heterodimer is captured in the act of 2'-O methylation of the ribose sugar of the first nucleotide of SARS-CoV-2 mRNA. We observe large conformational changes associated with substrate binding as the enzyme transitions from a binary to a ternary state. This induced fit model provides mechanistic insights into the 2'-O methylation of the viral mRNA cap. We also discover a distant (25 Å) ligand-binding site unique to SARS-CoV-2, which can alternatively be targeted, in addition to RNA cap and SAM pockets, for antiviral development.

PubMed: 32709886
DOI: 10.1038/s41467-020-17496-8

実験手法

X-RAY DIFFRACTION (1.8 Å)