A growing team of groundbreaking scientists around the world are now sharing their lab notebooks online
In this blog post, I will discuss the progress made on improving the binding affinity of new covalent quinazolines targeting CYS122, as well as some of the directions we are taking to further improve binding affinity to TBXT and reduce binding affinity towards EGFR. The synthetic work has been primarily driven by Zach and our Read More …
Our chordoma research focused on developing small reversible molecules targeting the transcription factor TBXT which codes for the brachyury protein. Brachyury contains several shallow pockets, and through an x-ray crystallography fragment based approach we previously identified several series of small fragments bound to it (TBXT Fragment Hits). Our medicinal chemistry project aimed to grow the Read More …
Our initial fragment screen identified four different fragments that bound to what we call site F (Figure 1) These can be found in the Protein Data Base (pdb) with these codes: 5QSA, 5QSC, 5QSI, and 5QSK. In this blog I will talk about some observations from these structures that suggest promise for this pocket, show Read More …
Biologists interested in the function or the 3D shape of a certain protein face the task of isolating billions of copies of that protein from cells (a process called “protein purification” which does not involve washing or holy water). The aim of protein purification is to start with cells that contain the protein of interest Read More …
Grin1 p.Tyr647Ser Project Background. Grin genes across species encode for proteins that make up the different NMDA receptor subunits. GRIN1 mutations (usually heterozygous) are associated with intellectual disability with epilepsy in humans, including the rare p.Tyr647Ser (Y647S) variant. This missense mutation occurs in the M3 helix of the transmembrane domain of GRIN1 which, importantly, is conserved between human GRIN1 and mouse Read More …
About one quarter of the Eukaryotic genome encodes glycoproteins that are made in the Endoplasmic Reticulum (ER), and travel to special destinations such as the extracellular environment, the cell membrane or other organelles like the lysosomes. We can think of the ER as a nursery where baby glycoproteins quickly grow to attain their adult Read More …
This is a test to figure out how we add links to zenodo lab notebooks, which are time stamped and have a DOI. I uploaded an image of our Sanger sequence that shows the introduction of base pair changes to cause an amino acid substitution Y647S. https://zenodo.org/record/3379009#.XWVmfpNKhp8
For the Ramsey Lab, this project began in 2018, when we were invited to a parent-organized meeting for caregivers of GRIN1 patients. Our group uses mice to study the NMDA receptor (which is encoded by the GRIN genes) in the context of schizophrenia and autism. It was only in 2018 that we learned of a Read More …
Nature has evolved molecules called glycoproteins that are proteins carrying sugar chains (“glycans”). Glycans can make proteins more soluble, they can shield them from the environment, they can be used as calling cards to enable protein-protein recognition; in Eukaryotes, a glucose-on/glucose-off quality control system uses glycans to monitor glycoproteins folding. In general, glycans contribute to Read More …
The inter-domain conformational mobility of UGGT, the eukaryotic secretion glycoprotein folding checkpoint, is likely key to its ability of recognising and re-glucosylating a vast number of different misfolded glycoproteins, bearing N-linked glycan(s) at various different distances from the site(s) of misfold. Ongoing Molecular Dynamics simulations by Juan Blanco, Carlos Modenutti, and Marcelo Martí in Buenos Read More …
