A protein kinase, an enzyme, might be the key to developing new cancer drugs according to a research study at the University of Arizona.
Protein Kinases work like switches that turn on and off certain cellular processes. If a cell's kinases stop working, the cell would die. Now, the University of Arizona (UA) research team has figured out the full pathway for activating a protein kinase. "Kinases are one of the major cancer drug targets,” explains senior author of the study and member of the UA BIO5 Institute and the UA Cancer Center, Wolfgang Peti. "If you know how a kinase works, you can definitely better design your drugs against it."
Creating a drug that utilizes these research findings will most likely take at least 10 years. However, there exists some cancer drugs already in use that target kinases. These drugs are dasatinib and imatinib for chronic myeloid leukemia (CML) and afatinib for non-small cell lung carcinoma (NSCLC).
Investigators used a nuclear magnetic resonance (NMR) spectroscopy to observe a particular protein kinase called mitogen-activated protein kinase (MAPK) p38 molecular pathway.
All crucial molecules had to bind to p38 for the kinase to be activated and exert its normal functions. "We figured out how it moves to do its job and what is the contribution of speed of movement to its job," Peti said. These research findings suggest a new route for developing anti-cancer drugs, and that is targeting the p38 pathway. "We are excited because this kinase belongs to a family of kinases that are called MAP kinases—key signaling kinases that regulate a plethora of pathways (within cells)," he said. This finding can also apply to other protein kinases
The idea is that enzymes can be thought of as a lock and a key. For example, a molecule can serve as the key when it fits into a site in the enzyme, which is serving as the lock. Once the key is in the lock, the enzyme can start working.
The key-in-the-lock is important for an enzyme to be activated, which isn't always easy. Some researchers proposed that that dynamics—the way and speed at which an enzyme moves—is necessary for activating kinase enzymes.
Peti is also interested in how kinases govern cellular processes, which inspired him to investigate the role of biochemical dynamics. Unfortunately, studying the role that dynamics plays in the activation of p38 was more difficult and took longer than expected.
