Cry-Electron Microscopy (cryo-EM) is a technology that allows for the visualization of proteins. Scientists broke through a technological barrier using this technology that will aid in drug discovery and development
National Cancer Institute’s (NCI) Sriram Subramaniam, Ph.D., led a research team that resulted in the picture taking of an enzyme found in cells, glutamate dehydrogenase, at a resolution of 1.8 angstroms. This level of detail has allowed for the structure of the central portion of the enzyme to be visualized in atomic detail.
Scientists from the National Center for advancing Translational Sciences (NCATS) provided contributions and aided to the discovery.
These advances benefit drug developers who could not potentially use cry-EM technology to modify drugs and witness the resulting change in structure, enabling a change or alternation in behavior for therapeutic effect.
Previously, the target proteins when bounded to drug candidates had to be coaxed to form arrarys. The traditional method of structure determination required the assembly of arrays so that X-ray crystallography could capture an image. An issue arose as not all proteins may form arrays easily and will not display the structure accurately.
Subramaniam stated that cry-EM technology allows for the structure determination of protein and potential drug candidates at a high level of detail. He believes this will “revolutionize and accelerate the drug discovery process.”
This study included the research on two small proteins, isocitrate dehydrogenase (IDH1) and lactate dehydrogenase (LDH), as they are active targets in terms of cancer drug development. The mutation of the genes that code for these specific proteins is found in several different types of cancer. Scientists hope to use this imaging to identify molecules that will bind to and turn off protein activity.
The journal Nature Methods titled cryo-EM technology as the “Method of the Year” this past January.