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How can hyperase protein activity be controlled to prevent it from assisting in the production of blood vessels for cancer tissue?

Dr. Gali Golan from the Hebrew University, who is doing a post-doctorate at the Rapoport Institute at the Technion and the Hebrew University, and is a recipient of the UNESCO-L'Oréal Award for Promising Sciences, talks about the protein that she studies using X-ray crystallography in order to know its three-dimensional structure, design materials for it that will affect its activity and help it To produce blood vessels in damaged limbs for diabetics, or prevent it from doing so in cancerous tissues

Right: CEO of L'Oreal Israel Nava Ravid, Dr. Gali Golan and Minister of Science Daniel Hershkowitz. Photography: Lem-Wlitz Studio
Right: CEO of L'Oreal Israel Nava Ravid, Dr. Gali Golan and Minister of Science Daniel Hershkowitz. Photography: Lem-Wlitz Studio

Crystallography of proteins. If this sounds familiar to you, then you were right, this is the field of research of Prof. Ada Yonat, winner of the Nobel Prize in Chemistry for 2009. But apart from the ribosome, which is a large protein molecule inside the cell, there is another variety of molecules in our body that need to be studied, among other things by the method of X-ray crystallography . This is the field of research of Dr. Gali Golan, who recently finished her doctoral thesis at the Hebrew University and is now conducting a joint post-doctorate for the Hebrew University and the Technion at the Rapoport Institute in Haifa.

Last week, Dr. Golan won one of two prizes awarded to promising scientists - the UNESCO L'Oréal Prize for Women in Science. "The truth is that X-ray crystallography is an amazing field. There is excitement because this is one of the only fields in science where you "see with your eyes" how a chemical reaction occurs between biological molecules, how catalysis occurs and how a molecule that is a drug is linked to an enzyme and inhibits it. "

Dr. Golan studies a certain protein called HEPARANASE. The heparin protein works in the intercellular medium and breaks down saccharide molecules that are in the intercellular matrix. When these molecules are released they play a role in their effect on tissue and blood vessel growth. "The heparin protein is an interesting target in the world of medicine because it affects many pathways: on the one hand, it affects cancer processes because a growing cancerous tissue requires the development of a branched system of blood vessels around it. Therefore, it is seen that in cancerous tissues there is a great activity of this protein that helps the cancer to grow. Therefore, when scientists today seek to develop inhibitors that will inhibit the activity of the enzyme in order to prevent the development of blood vessels into cancer. On the other hand, diabetics develop ulcers - whole areas of the body (mainly in the limbs) that have become necrotic. In this case, it is necessary to actually activate the protein so that it revives the tissue and helps it develop and not die."

Additional effects should be noted, among other things, in the reduction of hair roots. And so it is worthwhile to develop molecules that will help this enzyme to work. Frankincense also has an effect on intestinal diseases such as Crohn's and bowel cancer. Therefore it is very important to try to find the three-dimensional structure of the enzyme.

However, it is not so simple to perform crystallography for Franz. This is a problematic molecule for research because it is expressed in a limited number of developed organisms including humans, but not in bacteria for example. We need to make the body of the animal with which we want to study the protein overexpress it, and in a homogeneous and clean form, make it produce crystals and solve its three-dimensional structure. The goal beyond finding the three-dimensional structure is to design inhibitors that will bind to that enzyme (either polarize it or inhibit it) as needed. Once there is a structure for the enzyme it can affect a wide range of research areas and drug design.

The research is carried out in collaboration with Prof. Israel Valdavsky from the Rappoport Institute of Medicine (Technion) and the Structural Biology Unit at the Hebrew University, headed by Prof. Oded Livna. "I really hope that we will reach the breakthrough we are hoping for. As soon as the structure of the protein is solved, it will have a very big impact on the world of medicine."

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