There are approximately 75,000 different enzymes in the human body. These abundant proteins serve such a variety of roles in our bodies’ systems, we would truly not function the same without them. Nevertheless, enzymes can also become involved in the development of diseases such as Parkinson’s and even some cancer types.
One specific family of enzymes named the GTPases are often involved in these diseases. Science Direct classify GTPases as enzymes that facilitate the “conversion of guanosine triphosphate (GTP) to guanosine diphosphate (GDP).” Specifically, the reason this enzyme family has been historically deemed “undruggable” is related to the slippery exterior of the enzyme that made it difficult for modern drugs to target the disease-causing enzymes.
In September of 2024, researchers at the University of California San Francisco (UCSF) discovered a method for targeting the infamous K-Ras protein, a member of the GTPase family responsible for “up to 30% of all cancer cases.”
This enzyme and others like it work to regulate molecular movement and cell functions, so when an issue arises in these networks, diseases can easily develop. At UCSF, the team manipulated a K-Ras mutation to find new drug-binding sites that were previously unable to be seen by other drug discovery tools. Essentially, the mutation nudged open a pocket in the GTPases where the drug could bind, “freeze” the enzyme, and successfully inhibit a GTPase.
As we have learned in AP Biology, enzymes are globular proteins that are organic catalysts in living things. Enzymes work by lowering the amount of activation energy needed for a reaction to occur, and they do this by weakening the bonds between molecules and bringing them closer together to react with one another. Moreover, enzymes catalyze reactions by binding to one or more reactant molecules called substrates in the enzyme’s active site. This enzyme-substrate complex binds in a way that either a chemical bond-breaking or bond-forming process takes place, ending with the products of the reaction leaving the active site.
Meanwhile, enzyme inhibitors — such as the drugs studied by the UCSF researchers — can bind to the active site or another area of the enzyme and prevent the substrate(s) from binding and inhibit the reaction from happening.
According to the National Cancer Institute, an enzyme inhibitor is “a substance that blocks the action of an enzyme.” Relating to the significance of the researchers’ findings, this source explains that “In cancer treatment, enzyme inhibitors may be used to block certain enzymes that cancer cells need to grow.”
Groundbreaking research like this is becoming increasingly important for our understanding of the widespread diseases we face. Learning about the current innovative work of researchers is incredibly fascinating, as their work has significant implications for future enzyme research. It is truly exciting to see what researchers will investigate next in the field chemical genetics. What do you think will be the next step in enzyme research?
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