A growing team of groundbreaking scientists around the world are now sharing their lab notebooks online
X-ray crystallography is a tool used for the structural determination of proteins and biological molecules. My specific project focuses on the zinc finger ubiquitin binding domain (Zf-UBD) of USP5; however, USP5 is just one of many USPs that contain a Zf-UBD. Table 1 shows a list of the USP Zf-UBDs and their available structures in Read More …
Previously, I provided a brief overview on SCN1A related Dravet Syndrome (DS) and the need for larger gene therapy vectors or alternative methods to deliver functional copies of SCN1A to affected cells in DS. The goal of my project is to explore one of these alternative methods, specifically a split-intein mediated protein trans-splicing method, that Read More …
The goal of the Structural Genomics Consortium (SGC) is to discover and share selective small molecule inhibitors of protein kinases. Kinases have key roles in cell signaling, regulation of cell cycle progression, metabolism and other significant biological function. Cancers, immunological and metabolic diseases, among other ailments are caused by deregulation of kinase function. Protein kinases Read More …
So, the week has been super busy, but all for good reasons this time!! I’m absolutely thrilled to say that amongst all the salt crystals I found in my crystal plates, I also found the crystals below, one of which diffracted to 1.25 Å. This is definitely the highest resolution I’ve ever worked with. It’s amazing! Read More …
Hypothesis: Poly ADP ribose signaling is dysregulated in Huntington’s disease
Biophysical investigation of HTT and HTT-HAP40 using DSLS and SAXS
Takeaway: Why: we need lots of well diffracting crystals. How: crystallisation growth optimisation. What: tweaking conditions, phase space understanding, seeding, MMS. At this day and age (2018) many people are thinking that the future of structural molecular biology being about serial XFEL or synchrotron crystallography and electron diffraction, which are great tools to harness the Read More …
In my previous post, I described four promising fragments bound to HAO1 structures. Specifically, I described two key areas of HAO1 – the gating loop and active site Trp110 – where fragments 1, 2 and 5 bind. I also described fragment 6 at the subunit interface of HAO1, away from the active site. After analysis Read More …
As mentioned in my last post, I got 26 mg of ACVR1 on my last purification (as shown in my Zenodo log here). This is fabulous as it has allowed me to follow up a number of conditions for crystallisation. In particular, one of these hits was in G10 of my composite screen. I’ve therefore Read More …
I used a surface plasmon resonance assay to determine the binding affinities of hit compounds that were identified in 19F NMR spectroscopy screens against the zinc finger ubiquitin binding domain of USP5. To see how these assays work, check out some of my previous posts! You can see details of the SPR experiment on Zenodo. Read More …
