New Delhi, Jun 28 (KNN)In what may prove to be an important study, scientists have utilised neutron experiments to reveal in detail the function of an enzyme relevant for drug design against aggressive cancers. The finding could lead to new cancer therapies.
Uncovering the Enzyme’s Mysteries
Inhibition of serine hydroxymethyltransferase (SHMT), a metabolic enzyme essential for generating building blocks to advance cell division It is the enzyme targeted by the oncometabolite, and cancer cells seize this enzyme and send the entire metabolic process careening out of control to proliferate at a breakneck pace.
By conducting neutron experiments at the Department of Energy’s Oak Ridge National Laboratory, researchers have pinpointed the role of ions in the process to create SHMT on an atomic scale. A single amino acid residue—a glutamate—controls the function for this enzyme, they found. The dispute over this finding has lasted some decades, till the neutron data put paid to all. As for as this result is concerned, the part on hydrogen is interesting.
Using a combination of neutron and X-ray crystallography, the researchers mapped the protein structure of SHMT as well as how it interacted with tetrahydrofolate, an essential cofactor for this substrate. The identification of the positions of hydrogen atoms, which play a crucial role in much of chemistry, enabled the scientists to fully describe how the enzyme works.
Custom-Built Cancer Drug Faces Its First Test
This work may ultimately lead to improved cancer therapeutics due to the new insights about tumor-cell behavior that were revealed through the neutron experiments. With a specific knowledge of how SHMT functions, scientists may be able to design selective inhibitors that would prevent the enzyme from working and thus stop cancer from turning the metabolic pathway to its own use.
Other enzymes in the one-carbon metabolic pathway are already targeted by current cancer drugs such as methotrexate and fluorouracil, but those agents inhibit H3K27me3 levels. Instead, the conversion enzyme SHMT cooks up higher in this pathway — having a crucial molecular function that gives researchers hope for stopping cancer at an earlier step.
The researchers propose that most of their cancer studies have failed because cancer has the functional flexibility to adjust other metabolic pathways to maintain its high replication rate. The idea is to destroy cancer cells more quickly with fewer side effects on the patient by targeting SHMT.
Conclusion
Decades-old mystery of cancer cell metabolism finally solved Neutron studies open new possibilities for testing predictive cancer ‘omics The ground-breaking neutron experiments have definitively resolved the nearly 40-year-old debate over an enzymatic mechanism that had eluded teams from around the world. It also provides an opportunity to design targeted inhibitors capable of interfering with the ability of cancer cells to rapidly replicate, offering new chances for more effective and less damaging treatments.
