A growing team of groundbreaking scientists around the world are now sharing their lab notebooks online
My goal is to find druggable pockets in human enzymes that are non-catalytic. These non-catalytic druggable pockets may then be exploited for proximity pharmacology (ProxPharm), a novel paradigm in drug discovery where chimeric compounds bring two proteins in close proximity to elicit an effect of one protein on the other1. For example, PROTACs simultaneously bind Read More …
One of the important enzymes in the replication cycle of the SARS-CoV-2 virus is the helicase, which is also known as non-structural protein 13 (nsp13). During the viral life cycle, the holo-RNA-dependent RNA polymerase, also known as nsp12, is thought to coordinate with several additional factors, including the nsp13 helicase (Snijder et al., 2016; Sola Read More …
The RNA-dependent RNA-polymerase (RdRp) also known as non-structural protein 12 (nsp12) is the target of antiviral agent remdesivir. Nsp12 has an important role in viral genome replication and transcription. (Chen et al., 2020) Chen et al. identified a new pocket on the N-terminal extension of nsp12 occupied by ADP-Mg2+ after solving the structure of the helicase-polymerase complex. This ADP-bound pocket is on the N-terminal nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain which Read More …
This is an excerpt from my PhD thesis where I investigated 13 human PR/SET domains from the PRDM protein family and assessed their ability to bind to a fluorinated SAH analog. The research helps to identify which of the PRDMs could be methyltransferases. This work was carried out in the laboratory of Dr. Cheryl Arrowsmith Read More …
Production and purification of Ectodomain of SARS-CoV-2 Spike (S) protein Two different expression plasmids for prefusion S ectodomain residues 1−1208 of 2019-nCoV S (GenBank: MN908947) with proline substitutions (2P) at residues 986 and 987(1) and with six proline substitutions (HexaPro (at residues 817, 892, 899, 942, 986 and 987 (2), a “GSAS” substitution at the Read More …
In a previous post, I described a ubiquitin-rhodamine110 (UbRho110) assay, and showed that a ZnF-UBD ligand antagonizes USP5 catalytic activity. UbRho110 is not a native substrate, and validation with native polyubiquitin species in an orthogonal assay is required. To address this, I developed and optimized an internally quenched fluorophore pair (IQF) assay. You can see Read More …
SARS-CoV-2 is a positive-strand RNA virus, depending on its multi-subunit machinery to replicate its RNA. This machinery is known as RNA-dependent RNA polymerase (RdRp). The catalytic subunit of RdRp, which is the core component of this machinery, is called nsp12. Nsp12 has little catalytic activity on its own and relies on accessory subunits to have Read More …
