Modomics - A Database of RNA Modifications

ID Card:

Full name: Proofreading exoribonuclease nsp14
Structures: | 7DIY | 7EGQ | 7N0C | 7N0B | 7N0D |
Enzyme type: exoribonuclease, methyltransferase

PDB Structures:


Structure Description:


Abstract of the PDB Structure's related Publication:

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-α1', 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.

Download RCSB-PDB Structures:

Pdb Files   7DIY.pdb   7EGQ.pdb   7N0B.pdb   7N0C.pdb   7N0D.pdb  
Pdbx/mmCIF Files   7DIY.cif   7EGQ.cif   7N0B.cif   7N0C.cif   7N0D.cif  

Protein sequence:



Enzyme possessing two different activities: an exoribonuclease activity acting on both ssRNA and dsRNA in a 3' to 5' direction ( and a N7-guanine methyltransferase activity.


Title Authors Journal Details PubMed Id DOI
Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of Nsp14 RNA cap methyltransferase. Souradeep Basu,Tiffany Mak,Rachel Ulferts,Mary Wu,Tom Deegan,Ryo Fujisawa,Kang Wei Tan,Chew Theng Lim,Clovis Basier,Berta Canal,Joseph F Curran,Lucy S Drury,Allison W McClure,Emma L Roberts,Florian Weissmann,Theresa U Zeisner,Rupert Beale,Victoria H Cowling,Michael Howell,Karim Labib,John F X Diffley Biochem J [details] 34198328 -