SGC Univ. of Toronto

Calculating the change in Gibbs free energy (ddGbind) of an improved alpha-ketoamide inhibitor binding associated with genetic variations of SARS-CoV-2 main protease – post18

Posted onAuthorSetayesh YazdaniLeave a comment

Since we posted our analysis of genetic variation of SARS-CoV-2 main protease (MPro) with inhibitor N3 (PDB: 7bqy), there have been other inhibitors co-crystallized with the MPro (PDB: 6lze, PDB: 6m0k, and PDB: 6y2f). In my last post, I talked about the two inhibitors, 11a and 11b (PDB: 6lze, PDB: 6m0k) and in today’s post, Read More …

Back to SARS-CoV-2 Main Protease: Calculating the change in Gibbs free energy (ddGbind) of two peptidomimetic aldehyde Inhibitors binding associated with genetic variations of SARS-CoV-2 main protease – post17

Posted onAuthorSetayesh YazdaniLeave a comment

Since we posted our analysis of genetic variation of SARS-CoV-2 main protease (MPro) with inhibitor N3 (PDB: 7bqy), there have been other inhibitors co-crystallized with the MPro (PDB: 6lze and PDB: 6m0k). MPro acts like a scissor by cutting SARS-CoV-2 polyproteins into functional pieces, making it a critical target for antiviral therapies against SARS-CoV-2. In Read More …

Predicting the effect of all possible mutations at nsp3-Mac1 ADPr-binding site on ADPr binding – Post 16

Posted onAuthorSetayesh YazdaniLeave a comment

In my last post, I showed you the genetic variants at the ADP-ribose (ADPr) binding site of SARS-CoV-2 nsp3-Mac1 and the predicted effects of those mutations on ADPr binding with Mac1. Next, we wanted to assess the effect of all possible mutations at the sidechains lining the ADPr binding site of nsp3-Mac1 and how that Read More …

Genetic variability at the ADP-ribose Binding Site of the SARS-CoV-2 nsp3-Mac1 and predicted effects of mutations on ADP-ribose binding – Post 15

Posted onAuthorSetayesh YazdaniLeave a comment

In two of my previous posts 13 and 14, I showed how we found the residues lining the ADP ribose (ADPr) binding site of SARS-CoV-2 nsp3-Mac1 and we looked at the variability of this site across Alpha- and Betacoronavirus entries from UniProt. In addition to the UniPro sequences, we were interested in looking at variants Read More …

Mapping the genetic variations of Alpha- and Betacoronavirus UniProt entries onto SARS-CoV-2 nsp3-Mac1 crystal structure – Post 14

Posted onAuthorSetayesh YazdaniLeave a comment

In my last post, I showed how we found the residues lining the ADP-ribose (ADPr) binding site of SARS-CoV-2 nsp3-Mac1 using its crystal structure (PDB: 6w02). In this post, I will show the sequence diversity across UniProt entries from the Alpha- and Betacoronavirus genera and map that to the Mac1’s ADPr binding site using the Read More …

WDR5 and histone H3 interaction cell assay report

Posted onAuthorMagdalena SzewczykLeave a comment

  Background WDR5 belongs to the WD-repeat protein family and is an important component of various complexes, including SET1/MLL, NuRD, and NSL complex. It interacts with several binding partners via the “WDR5-interacting” (Win) site (e.g. symmetrically dimethylated histone H3R2, MLL1-4, SET1-2) or “WDR5-binding motif” (WBM) site (e.g. c,l,n-MYC, RBBP5). WDR5 emerged as a prime target Read More …

L3MBTL1 and histone H3 interaction cellular assay

Posted onAuthorMagdalena SzewczykLeave a comment

Background Malignant-Brain-Tumor (MBT) protein L3MBTL1 contains three tandem MBT repeats (3xMBT), which interact with mono- and dimethylated lysines of histone H4, H3 and H1.4 resulting in transcriptional repression. The interaction requires conserved aspartic acid (D355) in the second MBT repeat (PMID:17540172, 18408754, 20870725, 18408754). Assay validation Assay measuring the interaction of L3MBTL1 to histone H3 was Read More …

The next target: SARS-CoV-2 Macrodomain and Its Druggability – Post 13

Posted onAuthorSetayesh YazdaniLeave a comment

Previously we reported our analysis on the structural diversity of binding pockets found on the SARS-CoV-2 Main protease, methyltransferase, and papain-like protease. We then shifted our focus on the SARS-CoV-2 macrodomain (nsp3-Mac1). There are six macrodomain classes based on structural similarity. Most viral macrodomains fall into the MacroD-like family the same as human homologs MacroD1 Read More …

All possible mutations of residues lining the Papain-like protease catalytic site and their effects on VIR251-binding – Post 12

Posted onAuthorSetayesh YazdaniLeave a comment

In my last post, I showed you the genetic variants at the catalytic site of SARS-CoV-2 Papain-like protease (PLPro) and the predicted effects of those mutations on VIR251-binding. Next, we wanted to assess the effect of all possible mutations at the sidechains lining the catalytic site of PLPro and how that would affect VIR251-binding. VIR251 Read More …

Genetic variability at the catalytic site of the SARS-CoV-2 Papain-like protease and predicted effects of mutations on VIR251-binding – Post 11

Posted onAuthorSetayesh YazdaniLeave a comment

In two of my previous posts 9 and 10, I showed how we found the residues lining the catalytic pocket of SARS-CoV-2 Papain-like protease (PLPro) and we looked at the variability of this site across Alpha- and Betacoronavirus entries from UniProt. In addition to the UniPro sequences, we were interested in looking at variants from Read More …