Crystal Clear: Asia’s Advances In Structural Biology

Charu Chaudhry celebrates Asia’s many achievements in structural biology in the International Year of Crystallography.

AsianScientist (Feb. 5, 2014) – Seeing is believing, and no method has revealed more about the beautiful and hidden world of molecular structures than X-ray crystallography. 2014 marks the 100th anniversary of Max von Laue’s Nobel Prize awarded for the diffraction of X-rays by crystals. It is also the 400th anniversary of Kepler’s observation in 1611 of the symmetrical form of ice crystals, which began the broader studies of symmetry in matter.

Recognizing the fundamental importance of crystallography in science, biomedical research and society, the United Nations declared 2014 as the International Year of Crystallography (IYrC). IYCr2014 officially started with an opening ceremony at UNESCO headquarters in Paris on January 20 and 21, 2014.

The purpose of the IYrC is to raise public awareness, increase knowledge and instrumentation access in developing countries, inspire young scientists and foster international collaboration.

“[Throughout the year] we are conducting at least 15 to 20 open laboratories in less endowed regions of the world where students will have hands-on experience with crystallographic equipment and will be organizing three summit meetings that aim to bring together scientists and science administrators from countries that have been divided by geography, history, religion, politics and economics,” said Dr. Gautam Desiraju, president of the International Union of Crystallography (IUCr) and a professor at Indian Institute of Science Bangalore.

Among these, a summit meeting on Vistas in Structural Chemistry will be held on April 28 to 30 at the International Center for Chemical and Biological Sciences at the University of Karachi where the focus will be on the current and future state of scientific research in South and East Asia.

With rapid advances in DNA recombination technology, mass production of highly purified proteins, next-generation synchrotron radiation facilities and improved computational methods in the last decade, X-ray crystallography has become more widely accessible across the globe. This is reflected in the steady yearly increase in the number of crystal structures deposited in the Protein Data Bank (a global repository of 3D structural models), especially from Asia. Notably, of the 29 synchrotrons worldwide, eight are located in Asia, with Japan’s Spring-8 (Super Photon ring-8 GeV) leading the way as the world’s most powerful third generation synchrotron.

Behind these impressive statistics, labs throughput Asia have been pushing forward groundbreaking discoveries and cutting-edge research. For example, in 2005, Chinese research groups at Tsinghua University and the National Laboratory of Biomacromolecules (Institute of Biophysics, Chinese Academy of Sciences), determined the crystal structure of the mitochondrial respiratory membrane protein complex II, also known as mitochondrial succinate:ubiquinone oxidoreductase, a tour de force in biomolecular crystallography.

This macromolecular machine couples the Krebs cycle with the electron transport chain, producing most of the energy in eukaryotic cells. The structure was a marked breakthrough not only in crystallographic studies of membrane proteins, but also in the field of bioenergetics. Over the last decade or so, there have been many important structures coming out of Asia including influenza A virus, a plant light-harvesting complex, cytochrome c oxidase, bacteriorhodopsin, nicotinic acetylcholine receptor, aquaporin 1, a voltage-sensitive sodium channel and a glutamate transporter, to highlight a few.

Asian countries – including Japan, China, India and Korea – have also supported efforts in the worldwide structural genomics initiative – aimed at the large scale mapping of protein structure space by determining all the protein structures within selected genomes. Japan particularly has been a global leader in this area, initiating projects such as the RIKEN Structural Genomics Initiative as early as 1998 to determine bacterial, mammalian and plant protein structures.

Such projects also provide unprecedented opportunities for structure-based drug design and medicinal chemistry using high-throughput crystallography. Increasingly, industry-university-government collaborations in Asia are being explored for drug discovery innovation. Takeda, a large pharmaceutical company in Japan, has undertaken such open innovation collaborations.

Not all major discoveries need expensive equipment and huge teams of people, but rather just clear thought and vision. An example of a long-standing contribution to crystallography that highlights this is from G. N. Ramachandran, an Indian crystallographer and biophysicist, who questioned whether a polypeptide chain’s conformation may be restricted because the backbone is made of rigid planar peptide units. He was able to show that indeed there are limits imposed on polypeptide chain conformation by the need for non-bonded atoms to avoid bumping against each other. This was the genesis in 1963 of the Ramachandran plot of allowed peptide backbone geometries, which is still used today as the criteria to validate every protein structure.

As a final example of a more recent exciting methodological advance from Asia in 2013, Dr. Makoto Fujita’s research team at University of Tokyo developed a “crystal-free crystallography” method for small molecule (non-protein) structure determination. In this approach, a porous metal-organic framework serves as a crystalline ‘sponge’ with large well-defined internal cavities.

These scaffolds soak up small molecules so they become arranged in an orderly fashion, allowing their structures to be solved by X-ray crystallography. Many natural and synthetic compounds for which chemists have almost given up the hope of analyzing crystallographically can now be characterized by this method.

As we celebrate a century of crystallography, I cannot help but wonder what will the next 100 years look like. One thing is evident: it will challenge and capture our imaginations. And Asia will be at the frontlines. Happy brilliant one hundred!


Copyright: Asian Scientist Magazine.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

Charu Chaudhry is a Research Investigator at Bristol Myers Squibb USA in the Mechanistic Biochemistry, Lead Discovery and Optimization group . She has a PhD in Biophysics from Yale University and a BSc in Chemistry from MIT. She has a long-standing interest in understanding how proteins operate as molecular machines to perform essential functions in cells. Her current research focus is in biophysics and enzymology to support drug discovery across diverse therapeutic areas including immuno-oncology and fibrosis.

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