Brussels, 30 January 2002
Researchers at the European Molecular Biology Laboratory (EMBL) have produced a detailed diagram of a protein linked to leukaemia which gives researchers a head start in designing drugs to combat the disease.
Scientists developing drugs to combat disease typically work by finding drugs which work by blocking the activity of a particular molecule in a cell, like putting a lock over a switch. Now an EMBL team headed by Italian researcher Giulio Superti-Furga has produced a detailed diagram of the protein Abl, which is linked to certain forms of leukaemia. Using the information provided by the diagram, researchers now hope to custom design to block specific cellular 'switches.'
Abl is produced in all human cells, but some people acquire a defect in the genetic blueprint for the molecule, causing their bodies to create a malformed version called BCR-Abl, which is linked to certain forms of leukaemia. One of the main roles of the Abl protein is to send messages telling other molecules to divide. Normally, the number of times this message is sent is limited, but BCR-Abl and other defective forms of the protein get 'stuck' in transmission mode, leading to a very high rate of cell division and thus cancer.
'Abl needs to be switched off,' explained Giulio Superti-Furga, 'and one of the chief questions that people have had is whether other molecules are needed to throw the switch, or whether Abl can turn itself off. We've now discovered that there is an internal switch that allows it to shut itself down. BCR-Abl is missing an important structural piece of the protein, a sort of clamp that holds things in the right places, and the molecule can't stop sending signals.' The discovery is a significant starting point in designing drugs to treat leukaemia.
The researchers discovered that this clamp lies in a part of the molecule which is distant from the machinery which actually transmits the signals. They found the clamp by creating artificial versions of Abl missing certain parts, and then examining the molecule's transmitting capabilities in a test tube.
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