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2'-O methylation of RNA cap in SARS-CoV-2 captured by serial crystallography.
Wilamowski, Mateusz; Sherrell, Darren A; Minasov, George; Kim, Youngchang; Shuvalova, Ludmilla; Lavens, Alex; Chard, Ryan; Maltseva, Natalia; Jedrzejczak, Robert; Rosas-Lemus, Monica; Saint, Nickolaus; Foster, Ian T; Michalska, Karolina; Satchell, Karla J F; Joachimiak, Andrzej.
  • Wilamowski M; Center for Structural Genomics of Infectious Diseases, Consortium for Advanced Science and Engineering, University of Chicago, Chicago, IL 60637.
  • Sherrell DA; Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637.
  • Minasov G; Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology of Jagiellonian University, Krakow 30387, Poland.
  • Kim Y; Structural Biology Center, X-Ray Science Division, Argonne National Laboratory, Lemont, IL 60439.
  • Shuvalova L; Center for Structural Genomics of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
  • Lavens A; Center for Structural Genomics of Infectious Diseases, Consortium for Advanced Science and Engineering, University of Chicago, Chicago, IL 60637.
  • Chard R; Structural Biology Center, X-Ray Science Division, Argonne National Laboratory, Lemont, IL 60439.
  • Maltseva N; Center for Structural Genomics of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
  • Jedrzejczak R; Structural Biology Center, X-Ray Science Division, Argonne National Laboratory, Lemont, IL 60439.
  • Rosas-Lemus M; Data Science and Learning Division, Argonne National Laboratory, Lemont, IL 60439.
  • Saint N; Center for Structural Genomics of Infectious Diseases, Consortium for Advanced Science and Engineering, University of Chicago, Chicago, IL 60637.
  • Foster IT; Structural Biology Center, X-Ray Science Division, Argonne National Laboratory, Lemont, IL 60439.
  • Michalska K; Center for Structural Genomics of Infectious Diseases, Consortium for Advanced Science and Engineering, University of Chicago, Chicago, IL 60637.
  • Satchell KJF; Structural Biology Center, X-Ray Science Division, Argonne National Laboratory, Lemont, IL 60439.
  • Joachimiak A; Center for Structural Genomics of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
Proc Natl Acad Sci U S A ; 118(21)2021 05 25.
Article in English | MEDLINE | ID: covidwho-1223143
Preprint
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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 (m7GpppAm2'-O). Inhibition of Nsp16 activity may reduce viral proliferation, making this protein an attractive drug target.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA Caps / RNA, Messenger / RNA, Viral / SARS-CoV-2 Type of study: Experimental Studies Language: English Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA Caps / RNA, Messenger / RNA, Viral / SARS-CoV-2 Type of study: Experimental Studies Language: English Year: 2021 Document Type: Article