New drug target for treating deadly malaria identified

Researchers have revealed that a protein and other proteins it interacts with could become effective targets for new drugs to control the parasite that cause toxoplasmosis.

The researchers led by investigators at Indiana University School of Medicine determined that the protein, an enzyme called GCN5b, is necessary for the Toxoplasma parasite to replicate, so interfering with its activities could control the parasite.

GCN5b is part of the molecular machinery that turns genes on and off in the parasite, working with other proteins that, the researchers discovered, are more plant-like than their counterparts in humans.

"GCN5b is a very different protein than its human counterpart, and proteins it interacts with are not found in humans," William J. Sullivan Jr., Ph.D., associate professor of pharmacology and toxicology, said.

"That's what makes this exciting-rather than just having one enzyme that we could go after, there could be a whole collection of associated enzyme components that could be potentially targeted for drug therapies to control this parasite," he said.

In discovering that some of the proteins interacting with GCN5b are plant-like transcription factors-proteins that bind to DNA- the researchers filled in what had been a missing link explaining how the parasites control the process of turning genes on and off, known as gene expression.

The plant-like transcription factors recruit the GCN5b enzyme complex to activate a wide variety of genes for expression.

When the research team disabled the GCN5b complex, parasite replication swiftly came to a halt.

The study is published in the journal PLOS Pathogens.