Weizmann Institute Scientists Solve the 3-D Structure of the Enzyme involved in Gaucher Disease

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A team of scientists at the Weizmann Institute in Israel has solved the three-dimensional structure of the enzyme, glucocerebrosidase, which is deficient in sufferers of Gaucher disease. The scientists claim that the study, published recently in a journal of the European Molecular Biology Organisation (EMBO Reports), may lead to the design of new therapies for treating the disease.

'The first step in solving the three-dimensional structure of an enzyme or protein is to grow its crystals, ' says Prof Tony Futerman, of the Biological Chemistry Department at the Weizmann Institute, part the team of scientists who carried out this work. 'In the case of glucocerebrosidase, the crystallisation was a formidable challenge. We succeeded in doing this by trimming non-essential sugar com-ponents from the surface of the enzyme so that ordered crystals could be obtained.'

The scientists used X-ray crystallography, a method in which the crystal is exposed to X-rays and its structure determined by the diffraction pattern obtained. The X-ray data was collected at the European Synchrotron Radiation Facility in France.

Prof Futerman says: 'The solution of the enzyme structure may lead to the development of new therapies for Gaucher disease. 'First the structural information may help design a more effective enzyme that will improve today's enzyme replacement therapy.

'Also another type of therapy which may emerge from knowledge of the structure is the design of small molecules that may stabilise the defective enzyme in the patient, thereby restoring its function.

Prof Futerman added: 'A question now is whether we can interest a company to support the research needed to make better enzyme or small drugs that would eventually help Gaucher patients obtain better and possibly cheaper treatments'.

Prof Tony Futerman recently carried out research into the calcium connection with neuronopathic forms of Gaucher disease (reported in Gauchers News, March 2002.

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Source: Gauchers News October 2003.
© Copyright Gauchers Association Ltd 2003.