Key result
The crystal structure of mouse hepatitis virus nsp15 reveals a back-to-back hexamer functional unit and catalytic site, suggesting it as a new target for antiviral therapeutics.
The resolution of the MHV-A59 nsp15 hexameric structure and its catalytic site provides a novel target for the design of antiviral therapeutics against coronaviruses.
Answers are grounded in this paper and cite their sources.
Novel nsp15 fold enables inhibitor design; leaves open validation as antiviral target.
The unique coronavirus transcription/replication machinery comprised of multiple virus-encoded nonstructural proteins (nsp) plays a vital role during initial and intermediate phases of the viral life cycle. The crystal structure of mouse hepatitis virus strain A59 (MHV-A59) nsp15 is reported at 2.15-A resolution. nsp15 is an XendoU endoribonuclease and is the first one from this family to have its structure unveiled. The MHV-A59 nsp15 monomer structure has a novel protein fold. Two nsp15 trimers form a back-to-back hexamer that is believed to be the functional unit. The structure reveals the catalytic site including the highly conserved residues His262, His277, and Lys317, which is supported by mutagenesis analysis. Gel filtration and enzyme activity assays confirmed that the hexamer is the active form for nsp15 and demonstrate the specificity of nsp15 for uridylate. The high sequence conservation of nsp15 in coronaviruses, including that of severe acute respiratory syndrome, suggests that this protein may provide a new target for the design of antiviral therapeutics.
No takes yet. Share an insight, caveat, or question.
Xu et al. (2006) studied Coronavirus. The crystal structure of mouse hepatitis virus nsp15 reveals a back-to-back hexamer functional unit and catalytic site, suggesting it as a new target for antiviral therapeutics.
Synapse has enriched 10 related papers. Consider them for comparative context: