Journal: bioRxiv

Article Title: SARS-CoV-2 methyltransferase nsp10-16 in complex with natural and drug-like purine analogs for guiding structure-based drug discovery

doi: 10.1101/2024.03.13.583470

Figure Lengend Snippet: Structural representation of nsp10-16 with nsp10 as blue and nsp16 as beige surface (based on PDB entry: 7JIB). A) The active site is highlighted with a black frame and shows the substrates SAM and Cap0-analog as stick models with carbon in gray, oxygen in red, sulfur in yellow, nitrogen in blue, and phosphate in orange. B) Schematic representation of the active site with ligands as stick models as in A). The relative positions of the gate loops and the sub division of the Cap0 and SAM site is shown as described in the text. The extended cavity at the SAM site extends from N 7 at the adenosyl cavity.

Article Snippet: Briefly, His 6 -tagged nsp10-16 (expressed from HEK cells; commercially obtained from BPS Bioscience Catalog #100747) was labeled using the Monolith His-Tag Labeling Kit RED-Tris-NTA second generation (NanoTemper Technologies), according to the manufacturer’s instructions.

Techniques:

Journal: bioRxiv

Article Title: SARS-CoV-2 methyltransferase nsp10-16 in complex with natural and drug-like purine analogs for guiding structure-based drug discovery

doi: 10.1101/2024.03.13.583470

Figure Lengend Snippet: The compounds on top represent adenosine (green labels) and on the bottom tubercidin derivatives (blue labels). Structures of SARS-CoV-2 nsp10-16 with SAM, SAH, Sinefungin, WZ16 and SS148 have been described previously. The protein complex structures of the remaining compounds are reported in this study. Chemical differences of the derivatives compared to tubercidin are highlighted with green/blue circles or ellipsoids.

Article Snippet: Briefly, His 6 -tagged nsp10-16 (expressed from HEK cells; commercially obtained from BPS Bioscience Catalog #100747) was labeled using the Monolith His-Tag Labeling Kit RED-Tris-NTA second generation (NanoTemper Technologies), according to the manufacturer’s instructions.

Techniques:

Journal: bioRxiv

Article Title: SARS-CoV-2 methyltransferase nsp10-16 in complex with natural and drug-like purine analogs for guiding structure-based drug discovery

doi: 10.1101/2024.03.13.583470

Figure Lengend Snippet: A) Gate loop conformations for nsp16 with bound SAM (blue ribbon) in overlay with the SAM and Cap0-analog bound structure (green ribbon). SAM and Cap0-site positions are indicated by circles. B) Overlay of nsp10-16 structures with bound toyocamycin and Cap0-analog (yellow ribbon and sticks) with the structure resulting from soaking sangivamycin and Cap0-analog (pink ribbon and sticks). In the latter structure, SAM and SAH are present aside from sangivamycin and a fraction of the Cap0- analog was converted into Cap1. The orientation is identical to A). C) Interactions of Cap0-analog and toyocamycin (TO1) with nsp16. D) Interactions of SAH/sangivamycin (SGV) and Cap0/Cap1-analog with nsp16.

Article Snippet: Briefly, His 6 -tagged nsp10-16 (expressed from HEK cells; commercially obtained from BPS Bioscience Catalog #100747) was labeled using the Monolith His-Tag Labeling Kit RED-Tris-NTA second generation (NanoTemper Technologies), according to the manufacturer’s instructions.

Techniques: