Scientists at the Department of Energy's Oak Ridge National Laboratory have reported a breakthrough in understanding an enzyme's function that could lead to the development of new drugs for targeting aggressive cancers. The discovery centered on the enzyme serine hydroxymethyltransferase (SHMT), crucial for cell division and metabolic pathways that cancer cells exploit for rapid growth. Utilizing neutron scattering at facilities like the Spallation Neutron Source and the High Flux Isotope Reactor, the research team was able to determine specific atomic details that have been debated for over 40 years, according to the Oak Ridge National Laboratory.
In what can only be described as a significant advancement, researchers were able to observe within two neutron experiments the role of a glutamate residue in SHMT's activity. This residue, contrary to previous assumptions, maintains a proton which enables it to act as both an acid and a base in catalytic reactions. The Royal Society of Chemistry's journal Chemical Science recently published findings that hold promise to directly aid structure-based drug design. Lead author Victoria Drago from ORNL stated, "I think neutrons will be highly sought-after in future structure-based drug design," as per the Oak Ridge National Laboratory.
The enzyme SHMT plays a vital role in the one-carbon metabolism pathway within a cell's mitochondria, transforming the amino acid serine into glycine and contributing to the synthesis of DNA and RNA. By characterizing the enzyme's reaction mechanism with more precision, drug designers have a better target for developing inhibitors that could arrest the growth of cancer cells. As Dr. Andrey Kovalevsky, a co-author of the study, told ORNL, "The neutron data clearly show that the glutamate, which is an acid, has the proton on it." This level of detail is key for the rational design of drugs that can more effectively combat cancer.
With the rapid pace of scientific discovery, the implications of this research extend beyond immediate drug design and into the emerging use of artificial intelligence in medicine. William Nelson, director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, highlighted the potential future where, "with the help of AI, we will be able to sequence a gene in somebody's cancer, predict what the protein structure would look like and make a drug to tuck in," as stated by the ORNL.
