Nucleotide-bound crystal structures of the SARS-CoV-2 helicase NSP13

Acta Crystallogr F Struct Biol Commun. 2025 Aug 1;81(Pt 8):338-347. doi: 10.1107/S2053230X25005266. Epub 2025 Jul 10.

Abstract

Nucleotide-bound crystal structures of SARS-CoV-2 NSP13 in ADP- and ATP-bound states were resolved to 1.8 and 1.9 Å, respectively. The ADP-bound model captures a state immediately following ATP hydrolysis, with both ADP and orthophosphate still present in the active site. Further comparative analysis revealed that crystal packing influences NSP13 by stabilizing the nucleotide-binding site, underscoring the importance of accounting for these effects in structure-based drug design targeting NSP13.

Keywords: ADP-bound structure; ATP-bound structure; COVID-19; NSP13 helicase; SARS-CoV-2; inorganic phosphate; nucleotide-binding sites.

MeSH terms

  • Adenosine Diphosphate* / chemistry
  • Adenosine Diphosphate* / metabolism
  • Adenosine Triphosphate* / chemistry
  • Adenosine Triphosphate* / metabolism
  • Binding Sites
  • COVID-19 / virology
  • Catalytic Domain
  • Crystallography, X-Ray
  • Humans
  • Hydrolysis
  • Methyltransferases
  • Models, Molecular
  • Nucleotides / chemistry
  • Nucleotides / metabolism
  • Protein Binding
  • Protein Conformation
  • RNA Helicases* / chemistry
  • RNA Helicases* / metabolism
  • SARS-CoV-2* / chemistry
  • SARS-CoV-2* / enzymology
  • Viral Nonstructural Proteins* / chemistry
  • Viral Nonstructural Proteins* / genetics
  • Viral Nonstructural Proteins* / metabolism

Substances

  • Viral Nonstructural Proteins
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • Nsp13 protein, SARS-CoV
  • RNA Helicases
  • Nucleotides
  • Methyltransferases