X-ray crystallography is currently the most accurate technology for determining 3D structure of protein. It uses the ability of proteins to form crystals under specific conditions.
Molecules in the crystal form a very regular three-dimensional pattern, which upon being exposed to radiation of X-rays allows the registration of the diffraction pattern on a special detector. Such data is usually collected by synchrotron X-ray sources (available for example in Berlin – synchrotron BESSY). Analysis of the resulting images allows the researchers to determine the position of each of the thousands of atoms of the test substance with great precision, which makes it possible to create a three-dimensional model.
This level of observation of either the proteins or protein-ligand complexes makes crystallography one of the most advanced and promising approaches to new drugs discovery. Medications are often designed to block the activity of the protein (inhibitors), if the excess is the cause of the disease.
High resolution of the protein structure, which is a potential goal for therapy, allows for the design of specifically tailored chemical molecules that can interact with it.
This technique is also necessary to verify that the designed molecule combines with the protein as expected and that it has the potential to be used as a drug.
The use of crystallography is becoming a standard in the new drug creation. It often eliminates the cumbersome need of searching libraries of thousands, or millions of chemicals and tailoring them to a particular protein. This significantly limits the number of required experiments and greatly improves the final result of the project.
Crystallographic methods are the last and crucial stage of the cycle of work necessary to know the atomic structure of protein. Before starting the crystallization it is necessary to produce a very pure sample of a protein that has the appropriate concentration level.
First the gene of the target protein is optimized, usually for expression in bacterial cells (ie. the preparation of expression constructs – gene cloning), and then the gene is introduced into the cells which are then grown in bacterial cultures. During their growth the modified cells produce protein encoded by the introduced genetic information. A purified product is obtained through the extraction of cell biomass (ie. production and purification of recombinant proteins).
International Year of Crystallography 2014, UNESCO
Year 2014 has been declared by the General Assembly of the United Nations at the Year of Crystallography. The celebration is under a UNESCO international and International Union of Crystallography. At the inauguration of the Year of Crystallography Assoc. Marcin Nowotny – Head of the Protein Structure Laboratory at the International Institute of Molecular and Cell Biology in Warsaw was invited. It is a huge success for Dr. Nowotny and the Institute, since he was one of only 8 “talents” invited to participate in a special session for researchers specializing in crystallography. He represented not only the Institute and our country but also the entire region of Central – Eastern Europe. PhD.
Marcin Nowotny had a chance to present his achievements in front of a large group of very respectable community – including Irina Bokova – Director-General of UNESCO, Gautama R. Desiraju – President of the International Union of Crystallography and Brian K. Kobilką – winner of the Nobel Prize in chemistry. Thus, the world heard that in Warsaw advanced research in the field of crystallography is conducted and Polish scientists, specializing in this field, are strictly among the outstanding scholars of the world.