New 3D shapes of two proteins involved in stroke and cancer have been determined

A team of researchers led by Cardiff University has solved the 3D structures of two proteins involved in the regulation of blood pressure, stroke and cancer.

In humans, there has been growing evidence of the involvement of two proteins - SPAK and OSR1 - as key players in regulating blood pressure and their involvement in stroke. More recently they have also been reported to play an important role in breast cancer and so blocking the function of these enzymes could help in the treatment of these debilitating conditions.

Inspired by this knowledge the team, led by Dr Youcef Mehellou of the School of Pharmacy, has been working on developing new tools that could facilitate the discovery of new medicines to inhibit the function of SPAK and OSR1. Using a technique called protein crystallography they have mapped the 3D structure of the parts of the molecule that are critical to their function. With the shapes now known, the aim is to find drugs that can bind to these important areas. To do this, the team employed a new biophysical technique called CreoptixWAVE.

Together the results from this work, published in ChemBioChem, represent powerful resources that will accelerate the discovery of new molecules to potentially treat hypertension, stroke and breast cancer.

Dr. Mehellou said: “SPAK and OSR1 are involved in many serious diseases such as stroke and breast cancer. Our recent work will be instrumental in speeding up the process of targeting SPAK and OSR1 and discovering new medicines for these debilitating diseases.”

Further details on this study can be found here.