Brighton-led research pinpoints importance of ‘wobbly’ proteins
The research looked at why a protein that can play a key role in the development of cancer binds with drugs differently, depending on the amount of drug present.
The protein in question, NQO1, is already being investigated as a possible target for new cancer drugs as up to 25 percent of the human population can have too little of it which increases their chances of developing the disease. However, the protein has properties which mean that it binds differently to some anti-cancer drugs and the more of the drug present the less tightly the protein binds to the drug. This is known as ‘negative co-operativity’.
The research showed that this negative co-operativity does not occur if motion within the protein is modulated by altering its sequence. Amazingly, the researchers found that altering just one building block (a glycine amino acid in the middle of the protein) was enough to abolish negative co-operativity. This happens because this tiny change alters the overall ‘wobbliness’ of the protein. The findings could apply to other proteins and potentially lead to improvements in understanding a wide range of diseases.
Speaking about the research, Professor David Timson, Head of the School of Pharmacy and Biomolecular Sciences at the University of Brighton said: “It is already known that the lack of this protein can increase cancer risk. It is now known that this protein exhibits negative co-operativity with some anti-cancer drugs. Our research has now shed new light on why this is the case and established that by altering the ‘wobbliness’ of the protein we can change its properties and encourage it to bind with anti-cancer drugs more effectively.”
The research, which has been published in ChemBioChem, was carried out in collaboration with scientists from Queens University Belfast, Manchester University and Nottingham Trent University and funded by grants from the Medical Research Council and Association for International Cancer Research.