Growing co-crystallized fragments to ligands of the transcription factor brachyury (T)

In order to develop ligands addressing different possible binding sites of the transcription factor brachyury, fragments co-crystallized with this protein should be developed into ligands by using the program SparkTM (Cresset®). Brachyury (T, TBXT) is an essential regulator of the notochord development. Brachyury is primarily expressed in the embryo but not in the majority of normal Read More …

Re-Purification of ALK2 for crystallisation with different compounds from M4K.

I’ve been lucky enough to have a student (Mira) in the lab working with me for the past few weeks and so I’d like to write about the work that we’ve been doing together. We spent some time cleaning up an old sample of ALK2 that Ros had left over in the freezer to set Read More …

PhD position available in malaria parasite genomics and transcriptomics

Summary: –       3-year PhD funded by CNRS for genomics and transcriptomics data analysis of the Plasmodium falciparum malaria parasite. –       In a young dynamic team based in Montpellier, South of France, with many worldwide collaborators –       Keywords: population genetics & genomics, single-cell RNA-seq, molecular epidemiology, antigenic variation.   Our research Most malaria deaths are caused Read More …

Results from soaking follow-up compounds into preformed HAO1 crystals

In my last post, I told you I had soaked my follow-up compounds into HAO1 crystals to start developing structural explanations of how these compounds work. So far I have analysed four interesting protein-compound structures: 2 at the active site, 1 at the gating loop and 1 at the oligomeric interface. Full experimental details can Read More …

The Benefits of Conference attendance: BMP Signalling in Cancer II.

I’ve got a few things to catch up with on the blog – one of them is to talk about a conference I attended in Oxford recently. I attended the Biochemical Society BMP Signalling in Cancer II meeting which was held in St. Annes College, Oxford. At this meeting I presented a poster on the Read More …

Structure-Based PROTAC Design: Project Overview

Proteolysis Targeting Chimeras (PROTACs) are small molecules that induce the degradation of their target and have shown considerable promise as a novel therapeutic modality.1-3 PROTACs are heterobifunctional compounds containing one chemical moiety that binds to the target protein of interest and a chemical handle that binds to an E3 ubiquitin ligase (Figure 1). Recruitment of Read More …

Successful generation of fragments of the HTT protein and improving the purification procedure for the HTT-HAP40 complex

It has now been almost 2 years since I set out to try and make fragments of the huntingtin protein which might be amenable to structural analysis with X-ray crystallography. X-ray crystallography is a fantastic method and allows us to see the molecules in very fine atomic detail which is important if we are to Read More …

Determining whether bespoke tracers work with ALK5 in nanoBRET target engagement assay

Special thanks to: David Drewry – Helped with designing the nanoBRET tracers M4K pharma OICR chemist team – Synthesised the M4K1046-linker derivatives Carrow Wells (UNC) – Conjugated the M4K1046 to nanoBRET fluorophore Background: I have always wanted to establish nanoBRET target engagement assay for ALK5. Relative to dual luciferase promoter assay and immunofluorescent staining, nanoBRET Read More …