What is it about?

Proteins are complex molecular machines whose structure dictates thier capability to perform important biological functions, like catalyzing chemical reactions, replicating DNA, or transporting molecules. Some pharmaceutical drugs are small molecules that bind to proteins, controlling their structure and thus efficiency at performing these functions. However, most of these drugs are developed without full knowledge of the protein structure or binding because the process of determining this information using large crystals can require years of development. We demonstrate a way around this bottleneck by solving a bound protein structure using many small micron-sized protein crystals and microfluidic mixers.

Featured Image

Why is it important?

The use of many small crystals to solve the structure of a protein is a developing technique called serial crystallography. Before our manuscript, this method was only used to study protein binding dynamics at specialized facilities called X-ray Free-Electron Lasers. Our work demonstrates the technology to carry out these protein binding studies at synchrotron light sources, making these kind of studies widely available around the world. Furthermore, we show that the use of small crystals enables protein dynamics to be studied on timescales from milliseconds to seconds. This timescale is relevant for chemical binding and large-scale tertiary protein structure movements.

Perspectives

It is exciting to have contributed to the development of such a method because I think it has the possibility to change the pharmaceutical drug development cycle. The high-throughput nature of serial crystallography means that screening for drug binding can be as simple as flowing a different chemical into the mixer. Experiments like these can rapidly yield libraries of protein structures bound (or not) to different potential drug targets. This is a big step toward realizing structure-based drug development.

Kenneth Beyerlein
Max Planck Institute for the Structure and Dynamics of Matter

Read the Original

This page is a summary of: Mix-and-diffuse serial synchrotron crystallography, IUCrJ, October 2017, International Union of Crystallography,
DOI: 10.1107/s2052252517013124.
You can read the full text:

Read

Contributors

The following have contributed to this page