Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Weizmann institute scientists solve the 3-D structure of the enzyme involved in Gaucher disease

02.06.2003


Glucocerebrosidase


Discovery may help design effective therapies for the genetic disease that mainly affects Ashkenazi Jews

An interdisciplinary team of Weizmann Institute scientists has solved the three-dimensional structure of an enzyme called glucocerebrosidase. Mutations occurring in this enzyme cause Gaucher disease, a genetic illness that mainly affects Ashkenazi Jews. The Institute study, published recently in EMBO Reports, may lead to the design of effective new therapies for treating the disease.

Gaucher disease was first described in 1882 by the French physician Philippe Gaucher. It is characterized by swelling and enlargement of the spleen and liver and disruption in the function of these organs, and in rare cases it also affects the brain. In the 1920s, the disease was found to be caused by the excessive accumulation of a fatty substance, or lipid, called glucosylceramide. In the 1960s, researchers discovered that the accumulation occurs due to a defect in the glucocerebrosidase enzyme, whose function is to break down this lipid and regulate its amount. In the 1980s, the gene responsible for manufacturing the enzyme was isolated; scientists found that mutations in this gene disrupt the function of the enzyme, leading to the development of Gaucher disease.



By the early 1990s, the U.S. company Genzyme started producing the enzyme – first from placenta, then by genetic engineering. Today thousands of Gaucher patients are treated by injections of the enzyme, an approach called enzyme replacement therapy, or ERT. The annual cost of the therapy per patient is approximately $100,000 to $300,000. Obviously, more affordable alternatives, such as the ones that may emerge from the Weizmann Institute study, are urgently needed.

The Institute team included Prof. Tony Futerman of the Biological Chemistry Department, Prof. Joel Sussman of the Structural Biology Department and Prof. Israel Silman of the Neurobiology Department, as well as Dr. Michal Harel, Lilly Toker and graduate student Hay Dvir.

The first step in solving the three-dimensional structure of an enzyme is to grow its crystals. In the case of the glucocerebrosidase enzyme involved in Gaucher disease, the crystallization was a formidable challenge. The Weizmann Institute scientists succeeded in this task by cutting parts of certain sugar molecules on the surface of the enzyme.

The scientists then resorted to X-ray crystallography, a method in which the crystal is exposed to X-rays and the structure of its molecules is determined by the diffraction pattern of the X-rays. The X-ray data were collected at the European Synchrotron Radiation Facility in Grenoble, France.

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 ERT therapy. This approach is most likely to provide effective additional treatments for Gaucher disease, until the development of gene therapy for this disorder is developed. Another type of therapy likely to emerge from the Weizmann findings is the design of small molecules that will supplement the damaged enzyme in the patient’s body, thereby restoring its normal functioning.

Yeda Research and Development Co., which is responsible for the commercialization of Weizmann Institute research, has filed a patent application for the medical applications of these findings.

Prof. Futerman’s research is supported by The Estate of Ernst and Anni Deutsch-Promotor Stiftung, Switzerland, Paul Godfrey Foundation, and Buddy Taub Foundation. Prof. Futerman is the incumbent of the Joseph Meyerhoff Professorial Chair of Biochemistry.

Prof. Sussman’s research is supported by the Charles A. Dana Foundation, Jean and Jula Goldwurm Memorial Foundation, Helen & Milton A. Kimmelman Center for Biomolecular Structure & Assembly, Joseph and Ceil Mazer Center for Structural Biology, and The late Sally Schnitzer. Prof. Joel Sussman is the incumbent of the Morton and Gladys Pickman Chair in Structural Biology.

Prof. Israel Silman’s research is supported by Nella and Leon Benoziyo Center for Neurosciences, Charles A. Dana Foundation, Carl and Micaela Einhorn-Dominic Brain Research Institute, Helen & Milton A. Kimmelman Center for Biomolecular Structure & Assembly. Prof. Silman is the incumbent of the Bernstein-Mason Professorial Chair of Neurochemistry.


The Weizmann Institute of Science in Rehovot, Israel, is one of the world’s top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to 2,500 scientists, students, technicians and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials and developing new strategies for protecting the environment.

Alex Smith | EurekAlert!
Further information:
http://www.weizmann.ac.il/

More articles from Interdisciplinary Research:

nachricht The Internet of Things: TU Graz researchers increase the dependability of smart systems
18.02.2019 | Technische Universität Graz

nachricht Stanford researchers create a wireless, battery-free, biodegradable blood flow sensor
09.01.2019 | Stanford University

All articles from Interdisciplinary Research >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Revealing the secret of the vacuum for the first time

New research group at the University of Jena combines theory and experiment to demonstrate for the first time certain physical processes in a quantum vacuum

For most people, a vacuum is an empty space. Quantum physics, on the other hand, assumes that even in this lowest-energy state, particles and antiparticles...

Im Focus: Sussex scientists one step closer to a clock that could replace GPS and Galileo

Physicists in the EPic Lab at University of Sussex make crucial development in global race to develop a portable atomic clock

Scientists in the Emergent Photonics Lab (EPic Lab) at the University of Sussex have made a breakthrough to a crucial element of an atomic clock - devices...

Im Focus: Sensing shakes

A new way to sense earthquakes could help improve early warning systems

Every year earthquakes worldwide claim hundreds or even thousands of lives. Forewarning allows people to head for safety and a matter of seconds could spell...

Im Focus: A thermo-sensor for magnetic bits

New concept for energy-efficient data processing technology

Scientists of the Department of Physics at the University of Hamburg, Germany, detected the magnetic states of atoms on a surface using only heat. The...

Im Focus: The moiré patterns of three layers change the electronic properties of graphene

Combining an atomically thin graphene and a boron nitride layer at a slightly rotated angle changes their electrical properties. Physicists at the University of Basel have now shown for the first time the combination with a third layer can result in new material properties also in a three-layer sandwich of carbon and boron nitride. This significantly increases the number of potential synthetic materials, report the researchers in the scientific journal Nano Letters.

Last year, researchers in the US caused a big stir when they showed that rotating two stacked graphene layers by a “magical” angle of 1.1 degrees turns...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Modelica Conference with 330 visitors from 21 countries at OTH Regensburg

11.03.2019 | Event News

Selection Completed: 580 Young Scientists from 88 Countries at the Lindau Nobel Laureate Meeting

01.03.2019 | Event News

LightMAT 2019 – 3rd International Conference on Light Materials – Science and Technology

28.02.2019 | Event News

 
Latest News

Researchers measure near-perfect performance in low-cost semiconductors

18.03.2019 | Power and Electrical Engineering

Nanocrystal 'factory' could revolutionize quantum dot manufacturing

18.03.2019 | Materials Sciences

Long-distance quantum information exchange -- success at the nanoscale

18.03.2019 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>