2022
DOI: 10.1038/s41594-022-00828-1
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High-resolution structures of the SARS-CoV-2 N7-methyltransferase inform therapeutic development

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Cited by 16 publications
(24 citation statements)
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“…Very recently, several crystal structures of full-length nsp14 from SARS-CoV-2 were solved, bound to SAH (PDB 7R2V , 7QGI ) or to a cap-analogue (PDB 7QIF ) [ 27 , 28 ]. A high-resolution crystal structure of the SARS-CoV-2 N 7-MTase domain - expressed in fusion with the TELSAM epitope - was also reported [ 29 ]. These new structures provide crucial information for understanding the dynamics of nsp14 methyltransferase activity and pave the way for the structure-based development of new antivirals against CoVs.…”
Section: Introductionmentioning
confidence: 99%
“…Very recently, several crystal structures of full-length nsp14 from SARS-CoV-2 were solved, bound to SAH (PDB 7R2V , 7QGI ) or to a cap-analogue (PDB 7QIF ) [ 27 , 28 ]. A high-resolution crystal structure of the SARS-CoV-2 N 7-MTase domain - expressed in fusion with the TELSAM epitope - was also reported [ 29 ]. These new structures provide crucial information for understanding the dynamics of nsp14 methyltransferase activity and pave the way for the structure-based development of new antivirals against CoVs.…”
Section: Introductionmentioning
confidence: 99%
“…Data-processing and refinement statistics for this structure are given in Table 2. This observation suggests that fusion to 1TEL improved the resolution of vWa crystals produced in our hands by an average of 0.4 A ˚, a significant improvement (Table 1), providing an exciting hint into what more experienced crystallographers might be able to accomplish with TELSAM-mediated crystallization, such as in a recent stunning example involving the SARS-CoV2 nsp14 N7-methyltransferase domain (Kottur et al, 2022).…”
Section: A Bulkier Telsam-target Linker Did Not Alter the Crystalpack...mentioning
confidence: 63%
“…This parallels the experience of Kottur and coworkers, where three different linkers were tested in an attempt to crystallize the recalcitrant SARS CoV2 nsp14 N7-methyltransferase. In this case, only one of the three linkers resulted in crystals, but with optimization of the crystallization conditions the authors were able to reliably achieve a diffraction resolution of 1.4-1.6 A ˚ (Kottur et al, 2022).…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…The SARS-CoV-2 nsp14 MTase domain-encoding sequence (GenBank: YP 009725309.1, residues 300-527) was codon-optimized for expression in E. coli and synthesized by GeneArt (Thermo Scientific). The gene was cloned into a modified pRSFDuet vector containing an N-terminal hexahistidine (His6) purification tag, followed by a SUMO solubility and folding tag, and a TELSAM crystallization tag [38]. The plasmid was transformed into E. coli BL21 DE3 NiCo bacterial strain (New England Biolabs), and the protein was overexpressed using autoinduction ZY medium.…”
Section: Protein Expression and Purificationmentioning
confidence: 99%