6XKM

Room Temperature Structure of SARS-CoV-2 NSP10/NSP16 Methyltransferase in a Complex with SAM Determined by Fixed-Target Serial Crystallography

Summary for 6XKM

• Entry DOI: 10.2210/pdb6xkm/pdb
• Related: 6W4H 6WJT 6WKQ 6WQ3 6WRZ 6WVN
• Descriptor: 2'-O-methyltransferase, Non-structural protein 10, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: sars cov-2, serial crystallography, methyltransferase, s-adenosylmethionine, structural genomics, center for structural genomics of infectious diseases, csgid, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); More
• Total number of polymer chains: 2
• Total formula weight: 49267.40

Authors

Wilamowski, M.,Sherrell, D.A.,Minasov, G.,Kim, Y.,Shuvalova, L.,Lavens, A.,Chard, R.,Rosas-Lemus, M.,Maltseva, N.,Jedrzejczak, R.,Michalska, K.,Satchell, K.J.F.,Joachimiak, A.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2020-06-26, release date: 2020-07-08, Last modification date: 2023-10-18)

Primary citation

Wilamowski, M.,Sherrell, D.A.,Minasov, G.,Kim, Y.,Shuvalova, L.,Lavens, A.,Chard, R.,Maltseva, N.,Jedrzejczak, R.,Rosas-Lemus, M.,Saint, N.,Foster, I.T.,Michalska, K.,Satchell, K.J.F.,Joachimiak, A.
2'-O methylation of RNA cap in SARS-CoV-2 captured by serial crystallography.
Proc.Natl.Acad.Sci.USA, 118:-, 2021

PubMed Abstract: 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 (GpppA). Inhibition of Nsp16 activity may reduce viral proliferation, making this protein an attractive drug target.

PubMed: 33972410
DOI: 10.1073/pnas.2100170118

Experimental method

X-RAY DIFFRACTION (2.25 Å)