8CGB

Monkeypox virus VP39 in complex with SAH

8CGB の概要

• エントリーDOI: 10.2210/pdb8cgb/pdb
• 分子名称: Cap-specific mRNA (nucleoside-2'-O-)-methyltransferase, S-ADENOSYL-L-HOMOCYSTEINE (3 entities in total)
• 機能のキーワード: methyltransferase, ligand, monkeypox virus, transferase
• 由来する生物種: Monkeypox virus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 72283.39

構造登録者

Silhan, J.,Klima, M.,Skvara, P.,Boura, E. (登録日: 2023-02-03, 公開日: 2023-04-26, 最終更新日: 2024-06-19)

主引用文献

Silhan, J.,Klima, M.,Otava, T.,Skvara, P.,Chalupska, D.,Chalupsky, K.,Kozic, J.,Nencka, R.,Boura, E.
Discovery and structural characterization of monkeypox virus methyltransferase VP39 inhibitors reveal similarities to SARS-CoV-2 nsp14 methyltransferase.
Nat Commun, 14:2259-2259, 2023

PubMed Abstract: Monkeypox is a disease with pandemic potential. It is caused by the monkeypox virus (MPXV), a double-stranded DNA virus from the Poxviridae family, that replicates in the cytoplasm and must encode for its own RNA processing machinery including the capping machinery. Here, we present crystal structures of its 2'-O-RNA methyltransferase (MTase) VP39 in complex with the pan-MTase inhibitor sinefungin and a series of inhibitors that were discovered based on it. A comparison of this 2'-O-RNA MTase with enzymes from unrelated single-stranded RNA viruses (SARS-CoV-2 and Zika) reveals a conserved sinefungin binding mode, implicating that a single inhibitor could be used against unrelated viral families. Indeed, several of our inhibitors such as TO507 also inhibit the coronaviral nsp14 MTase.

PubMed: 37080993
DOI: 10.1038/s41467-023-38019-1

実験手法

X-RAY DIFFRACTION (2.47 Å)