Purification and crystallisation of ALK2 (R206H mutation) with M4K Pharma compounds.

As part of an ongoing collaboration with Meds4Kids Pharma (M4KPharma), we are testing a range of compounds identified and generated by them as being of interest in developing a molecule specific against ALK2 that has the right properties help treat some cases of DIPG. This also has significant implications for development of a drug that Read More …

Pull down of XIAP with type I & II receptors. Tm shifts of M4K Pharma compounds with Alk2, Alk5 and RIPK2.

XIAP and its interaction with type I and type II receptors. Having spent time over the past few weeks purifying all the components needed for a pull down with XIAP, I did the experiment that looked for interactions between XIAP and various type I and type II receptors in both the un-phosphorylated and phosphorylated form. Read More …

Protein purification and Tm shift experiments.

Purification of proteins for a pull down experiment between XIAP and various type I and type II receptors. XIAP is known to bind to the kinase RIPK2. RIPK2 is one of the few kinase proteins that shows overlap of reactivity to some of the compounds that we’ve been looking at in the context of ALK2 Read More …

Structure deposition of ALK2 structures and structural analysis of ALK2/FKBP12 complex with PK010710 and PK012055

Deposition: In the past two weeks my work has mostly been full of dealing with structures. The first thing I needed to do was deposit some structures of ALK2 co-crystallised with three drug molecules that I had solved for our collaborators Swen Hoelder and Liam Hudson at ICR, who had been developing compounds against ALK2. Read More …

Crystal mounting of ALK2 with FKBP12 and six compounds with subsequent data collection

One of the more unpredictable parts of crystallography is also one of the most fundamental – will the protein crystallise? Despite decades of work done on protein crystallisation, and numerous ‘tricks of the trade’ to maximise the chances, whether a protein will actually form a crystal is still relatively random.  With ALK2 we’ve crystallised it Read More …

Co-Crystallisation of the ALK2/FKBP12 complex with compounds from M4K and others.

New compounds developed by Meds4Kids (M4K) and other collaborators against ALK2 would benefit from being crystallised so we can look at the structure of the complex and explain exactly how these compounds bind. This helps us work out how to improve them for both potency and selectivity and explain why some bind better than others. Read More …

Project overview: New compounds for FOP and the role of mutation on protein function.

Hi, my name is Ellie Williams and I’ve been working at the SGC since 2010 in the lab of Alex Bullock. I’m funded by FOP Friends to look at the development of new drugs that target ALK2 and to study the disease Fibrodysplasia Ossificans Progressiva (or FOP). In the last couple of years a new Read More …