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10.1093/nar/gkab320

http://scihub22266oqcxt.onion/10.1093/nar/gkab320
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33956156!8136770!33956156
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suck abstract from ncbi


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pmid33956156      Nucleic+Acids+Res 2021 ; 49 (9): 5382-5392
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  • Crystal structure of SARS-CoV-2 nsp10 bound to nsp14-ExoN domain reveals an exoribonuclease with both structural and functional integrity #MMPMID33956156
  • Lin S; Chen H; Chen Z; Yang F; Ye F; Zheng Y; Yang J; Lin X; Sun H; Wang L; Wen A; Dong H; Xiao Q; Deng D; Cao Y; Lu G
  • Nucleic Acids Res 2021[May]; 49 (9): 5382-5392 PMID33956156show ga
  • The emergence of SARS-CoV-2 infection has posed unprecedented threat to global public health. The virus-encoded non-structural protein 14 (nsp14) is a bi-functional enzyme consisting of an exoribonuclease (ExoN) domain and a methyltransferase (MTase) domain and plays a pivotal role in viral replication. Here, we report the structure of SARS-CoV-2 nsp14-ExoN domain bound to its co-factor nsp10 and show that, compared to the SARS-CoV nsp10/nsp14-full-length complex, SARS-CoV-2 nsp14-ExoN retains an integral exoribonuclease fold and preserves an active configuration in the catalytic center. Analysis of the nsp10/nsp14-ExoN interface reveals a footprint in nsp10 extensively overlapping with that observed in the nsp10/nsp16 structure. A marked difference in the co-factor when engaging nsp14 and nsp16 lies in helix-alpha1', which is further experimentally ascertained to be involved in nsp14-binding but not in nsp16-engagement. Finally, we also show that nsp10/nsp14-ExoN is enzymatically active despite the absence of nsp14-MTase domain. These data demonstrate that SARS-CoV-2 nsp10/nsp14-ExoN functions as an exoribonuclease with both structural and functional integrity.
  • |*Biocatalysis[MESH]
  • |Binding Sites[MESH]
  • |Crystallography, X-Ray[MESH]
  • |Exoribonucleases/*chemistry/genetics/*metabolism[MESH]
  • |Guanine[MESH]
  • |Methyltransferases/chemistry/deficiency/genetics/metabolism[MESH]
  • |Models, Molecular[MESH]
  • |Protein Domains/genetics[MESH]
  • |SARS-CoV-2/*chemistry/*enzymology/genetics[MESH]
  • |Viral Nonstructural Proteins/*chemistry/genetics/*metabolism[MESH]


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