Researchers at the University of Missouri have identified a new chemical compound named MKV3 that targets natural copper transport proteins in human cells, bacteria, and other organisms, according to a study published in the Proceedings of the National Academy of Sciences. The discovery offers a potential new avenue for treating antibiotic-resistant infections and targeting cancer cells by manipulating how cells regulate copper.
How MKV3 Disrupts Cellular Copper Transport
Copper is an essential nutrient for cellular function, but excessive amounts become toxic. To maintain balance, cells utilize specialized transport proteins to move copper in and out. According to Michael Petris, a professor of biochemistry at the University of Missouri and senior author of the study, MKV3 blocks a key type of copper transport protein. This action disrupts both the delivery of copper to enzymes that require it and the export of excess copper from cells.
Kamal Singh, an assistant professor of veterinary pathobiology at the university and co-author of the study, used computer modeling to design the drug candidate. Laboratory testing subsequently confirmed that the compound functions as predicted by inhibiting targeted protein mechanisms.
Combating Antibiotic-Resistant Infections
Pathogenic bacteria depend on copper-export systems to survive immune system attacks. During an infection, the human immune response deploys high levels of copper to destroy invading microbes, prompting bacteria to pump the excess metal out of their cells.
According to the University of Missouri research team, MKV3 inhibits these bacterial copper export pumps, which leaves the pathogens vulnerable to copper toxicity. In laboratory tests, the compound made methicillin-resistant Staphylococcus aureus (MRSA)—widely recognized as a difficult-to-treat antibiotic-resistant bacterium—significantly more susceptible to copper. Petris noted that targeting copper transport could emerge as a novel strategy to help the human body fight drug-resistant infections.
Implications for Cancer Treatment
The discovery also impacts cancer research, where cellular copper metabolism is increasingly viewed as a therapeutic target. Vinit Shanbhag, an assistant research professor and lead author of the study, explained that MKV3 attacks cancer cell dependencies in two distinct ways within laboratory cultures.
“In cultured cancer cells, it caused copper to accumulate, increasing sensitivity to cuproptosis, a form of cell death caused by copper,” Shanbhag stated. Simultaneously, the compound reduced the activity of lysyl oxidase by restricting copper delivery to that specific enzyme, which is associated with tumor invasion and metastasis. These findings support ongoing investigation into MKV3 as a potential cancer treatment strategy.
A Conserved Mechanism Across Species
The study demonstrated that MKV3 affects copper transport proteins across a broad range of organisms, including mammals, fungi, plants, fish, and disease-causing microbes. According to researchers, the compound targets a binding pocket that is conserved in copper transporters across species separated by millions of years of evolution. This provides scientists with a chemical tool to study identical fundamental transport mechanisms in multiple life forms.
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