7ctt

Electron Microscopy
3.2Å resolution

Cryo-EM structure of Favipiravir bound to replicating polymerase complex of SARS-CoV-2 in the pre-catalytic state.

Released:
Primary publication:
Structural Basis of SARS-CoV-2 Polymerase Inhibition by Favipiravir.
OpenAccess logo Innovation (Camb) 2 100080 (2021)
PMID: 33521757
Related structures: EMD-30469

Function and Biology Details

Reactions catalysed:
S-adenosyl-L-methionine + a 5'-(5'-triphosphoguanosine)-[mRNA] = S-adenosyl-L-homocysteine + a 5'-(N(7)-methyl 5'-triphosphoguanosine)-[mRNA]
S-adenosyl-L-methionine + a 5'-(N(7)-methyl 5'-triphosphoguanosine)-(ribonucleotide)-[mRNA] = S-adenosyl-L-homocysteine + a 5'-(N(7)-methyl 5'-triphosphoguanosine)-(2'-O-methyl-ribonucleotide)-[mRNA]
Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1)
GTP + a 5'-diphospho-[mRNA] = diphosphate + a 5'-(5'-triphosphoguanosine)-[mRNA]
Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).
TSAVLQ-|-SGFRK-NH(2) and SGVTFQ-|-GKFKK the two peptides corresponding to the two self-cleavage sites of the SARS 3C-like proteinase are the two most reactive peptide substrates. The enzyme exhibits a strong preference for substrates containing Gln at P1 position and Leu at P2 position.
ATP + H(2)O = ADP + phosphate
Biochemical function:
Biological process:
Cellular component:
  • not assigned

Structure analysis Details

Assembly composition:
hetero hexamer (preferred)
PDBe Complex ID:
PDB-CPX-145050 (preferred)
Entry contents:
3 distinct polypeptide molecules
2 distinct RNA molecules
Macromolecules (5 distinct):
RNA-directed RNA polymerase nsp12 Chain: A
Molecule details ›
Chain: A
Length: 932 amino acids
Theoretical weight: 106.78 KDa
Source organism: Severe acute respiratory syndrome coronavirus 2
Expression system: Spodoptera aff. frugiperda 1 BOLD-2017
UniProt:
  • Canonical: P0DTD1 (Residues: 4393-5324; Coverage: 13%)
Gene names: 1a-1b, rep
Sequence domains:
Non-structural protein 8 Chains: B, D
Molecule details ›
Chains: B, D
Length: 198 amino acids
Theoretical weight: 21.9 KDa
Source organism: Severe acute respiratory syndrome coronavirus 2
Expression system: Escherichia coli
UniProt:
  • Canonical: P0DTD1 (Residues: 3943-4140; Coverage: 3%)
Gene names: 1a-1b, rep
Sequence domains: Coronavirus replicase NSP8
Non-structural protein 7 Chain: C
Molecule details ›
Chain: C
Length: 83 amino acids
Theoretical weight: 9.25 KDa
Source organism: Severe acute respiratory syndrome coronavirus 2
Expression system: Escherichia coli
UniProt:
  • Canonical: P0DTD1 (Residues: 3860-3942; Coverage: 1%)
Gene names: 1a-1b, rep
Sequence domains: Coronavirus replicase NSP7
Primer-RNA (5'-R(P*UP*UP*CP*UP*CP*CP*UP*AP*AP*GP*AP*AP*GP*CP*UP*A)-3') Chain: Q
Molecule details ›
Chain: Q
Length: 20 nucleotides
Theoretical weight: 6.33 KDa
Template-RNA (5'-R(P*AP*CP*UP*AP*GP*CP*UP*UP*CP*UP*UP*AP*GP*GP*AP*GP*AP*A)-3') Chain: T
Molecule details ›
Chain: T
Length: 40 nucleotides
Theoretical weight: 12.7 KDa

Ligands and Environments

3 bound ligands:
No modified residues

Experiments and Validation Details

Entry percentile scores
Resolution: 3.2Å
Relevant EMDB volumes: EMD-30469
Expression systems:
  • Spodoptera aff. frugiperda 1 BOLD-2017
  • Escherichia coli