8B07

Crystal structure of monkeypox virus methyltransferase VP39 in complex with sinefungin

Summary for 8B07

• Entry DOI: 10.2210/pdb8b07/pdb
• Descriptor: Cap-specific mRNA (nucleoside-2'-O-)-methyltransferase, SINEFUNGIN (3 entities in total)
• Functional Keywords: viral, methyltransferase, vp39, monkeypox, capping, enzyme, viral protein
• Biological source: Monkeypox virus (monkeypox)
• Total number of polymer chains: 2
• Total formula weight: 72661.76

Authors

Silhan, J.,Klima, M.,Boura, E. (deposition date: 2022-09-07, release date: 2023-04-05, Last modification date: 2024-02-07)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.05 Å)