April 7, 2024
BADEN, April 7, 2024 - On the World Health Day, we commemorate the global impact of our technology, enabling structural biologists worldwide to make important breakthroughs in public health.
Since the first PILATUS X-ray detector revolutionized biological research at synchrotron light sources over fifteen years ago, progress in life sciences, drug discovery and drug development accelerated, including the development of vaccines. This faster, more structure-based approach to do biological research led to many important discoveries. As a pioneering technique in Structural Biology, Macromolecular Crystallography functioned as a catalyst for scientists to identify the structures of macromolecules, such as proteins, DNA, or RNA. Determining the macromolecules’ structures is key for understanding their biological function, and therefore for aiding drug design and development.
DECTRIS Ltd, global developer and manufacturer of Hybrid Photon Counting detectors for X-ray and Electron Microscopy research, has enabled with its two detector series, PILATUS and EIGER, the determination of around 59,000 structures in total. In 2023, 81% of the X-ray structures deposited in the Protein Data Bank (PDB) were collected with these detectors, as compared to those that were identified using other X-ray detection technologies (CCD or CMOS). To celebrate World Health Day, we want to commemorate the impact of this leading application of X-ray research in the field of Life Sciences, and to describe its use in academic and private laboratories before samples are studied in more detail at synchrotrons.
In the pharmaceutical industry, powerful laboratory diffractometers are essential for pharmaceutical research, development and quality control during production. They allow for all aspects of the experiment to be under full control and for decisions to be made quickly. Among others, Astex Pharmaceutical in the UK, Array Biopharma in the US, and Novo Nordisk in Denmark are all productive with state-of-the-art diffractometers with EIGER R 1M or PILATUS3 R 1M detectors.
In drug development, researchers from the laboratory of Prof. Martin Safo at Virginia Commonwealth University studied the structure-function relationship of hemoglobin. Their goal was to develop an anti-sickling agent against sickle cell disease, a hereditary blood disorder that is associated with anemia, infections, episodes of pain, and delayed growth and development.
The fight against Trypanosoma diseases, such as sleeping sickness, Chagas’ disease, and leishmaniasis also requires X-ray research in laboratories. These diseases, which pose serious health problems in developing countries, are caused by trypanosomes, protozoans characterized by a unique trypanothione redox system. Prof. Emil Pai‘s group in a laboratory at the University of Toronto studied trypanothione reductase inhibitors, an attractive class of ligands that is inactive against organisms with conventional glutathione redox systems.
Drugs for fighting blood cancers can also be designed after structural enzymology studies. Dr. Alexander Wlodawer’s team in a laboratory at the National Cancer Institute in Frederick studied the catalytic mechanism of L-asparaginases. These are enzymes that catalyze the hydrolysis of the amino acid asparagine into aspartate. They are clinically important for the treatment of certain leukemias and lymphomas.
To summarize, Macromolecular Crystallography is a powerful technique that facilitates research on molecules, from their structure and function to the design of suitable drugs. Together with the evolution of other Structural Biology methods, Macromolecular Crystallography will continue to advance research in Life Sciences and in the pharmaceutical industry.
About DECTRIS
DECTRIS develops and manufactures the most accurate X-ray and electron cameras to spark scientific breakthroughs around the world. While photographic cameras capture visible light, DECTRIS cameras count individual X-ray photons and electrons. DECTRIS is the global market leader at synchrotrons. Our efficient detector systems help scientists achieve high-quality results also in their laboratories. Our detectors played for example a decisive role in the determination of the structures of the coronavirus. The DECTRIS electron detectors create unique opportunities in material science, and we offer novel solutions for medical applications. We support researchers everywhere from our offices in Switzerland, Japan and the United States.
About this article
Parts of this article were written by DECTRIS former structural biochemist Andreas Förster in February 2020, a year before he sadly passed away after losing his battle against cancer. By bringing his research back four years after, we also pay tribute to him and to his important contributions in the field of crystallography and structural biology.
About Macromolecular Crystallography
Macromolecular Crystallography (MX) is the most powerful method for determining the three-dimensional structures of biological macromolecules. It tends to achieve the highest-resolution information and gives the most reliable structures, while not suffering from limitations on sample size - as long as crystals are available.
Contact Information
Press Contact
Dr. Clara Demin
Senior Communications Manager
+41 (0) 56 500 31 51
Contact for interview
Dr. Sofia Trampari
Application Scientist, X-Ray Crystallography
sofia.trampari@dectris.com
References
Structural biology in the pharmaceutical industry
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Sickle-cell disease
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P. P. Pagare et al., Bioorganic & Medicinal Chemistry. 26, 2530-2538 (2018)
6DI4, 6BNR, 6BWP, 6BWU (EIGER R 4M).
Trypanosoma diseases
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R. De Gasparo et al., Chemistry-A European Journal. 25, 11416-11421 (2019)
L-asparaginases:
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J. Lubkowski et al., Protein Science. 28, 1850-1864 (2019)
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J. Lubkowski et al., Scientific Reports. 9 (2019)
