2'-O methylation of RNA cap in SARS-CoV-2 captured by serial crystallography.

The genome of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronavirus has a capping modification at the 5'-untranslated region (UTR) to prevent its degradation by host nucleases. These modifications are performed by the Nsp10/14 and Nsp10/16 heterodimers using S-adenosylmethionine as the methyl donor. Nsp10/16 heterodimer is responsible for the ...
methylation at the ribose 2'-O position of the first nucleotide. To investigate the conformational changes of the complex during 2'-O methyltransferase activity, we used a fixed-target serial synchrotron crystallography method at room temperature. We determined crystal structures of Nsp10/16 with substrates and products that revealed the states before and after methylation, occurring within the crystals during the experiments. Here we report the crystal structure of Nsp10/16 in complex with Cap-1 analog (m7GpppAm2'-O). Inhibition of Nsp16 activity may reduce viral proliferation, making this protein an attractive drug target.
Mesh Terms:
Crystallography, Methylation, Methyltransferases, Multiprotein Complexes, RNA Cap Analogs, RNA Caps, RNA, Messenger, RNA, Viral, S-Adenosylhomocysteine, S-Adenosylmethionine, SARS-CoV-2, Synchrotrons, Viral Nonstructural Proteins, Viral Regulatory and Accessory Proteins
Proc Natl Acad Sci U S A
Date: Dec. 25, 2020
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