Phosphorylation of SMAD1 – rates as a function of Alk2 mutations and type II association.

One of the questions to be asked when looking at the mutation in ALK2 that causes FOP, is how exactly does that mutation cause the disease. ALK2 we know is part of the BMP signalling pathway responsible for bone formation and the mutation results in excess bone formation – thus we can summarise that somehow Read More …

Screening follow up compounds from active site and gating loop HAO1 fragment hits

In my previous post, I confirmed that the two active site fragments (fragments 1 and 2) and the gating loop fragment (fragment 5) bind to and inhibit HAO1 in solution. Next, I chose some larger compounds to test by entering each fragment hit structure into a search engine (emolecules.com) to look for commercially available compounds Read More …

USP Zf-UBD Crystallography Pipeline

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 …

Design of split-intein mediated SCN1A protein trans-splicing

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 …

Introduction to CaMKK2: Goals and previous work

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 …

Some good news! I have data! Not just any data – 1.25 Å data!

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 …

How high throughput fragment screening is reviving old school crystallography tricks

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 …