Researchers Successfully Map Enzyme Involved in Multiple Diseases

Discovery may lead to development of new drugs to treat parasitic diseases.

Researchers recently mapped the structure of an enzyme that may lead to the creation of new drugs to treat 3 diseases common in developing areas of the world.

The enzyme, fumarate hydratase (FH), is critical for the metabolic process of parasites that cause Leishmaniases, Chagas disease, and sleeping sickness. By identifying FH’s structure, researchers could discover ways to inhibit the enzymes and create new medical treatments, according to a study published by the Proceedings of the National Academy of Sciences.

"This enzyme is really critical for the metabolism of organisms like Leishmania major,” said researcher Catherine Drennan, PhD. “If you knock it out, the organism should be dead."

Leishmaniases are a group of diseases known to cause varying conditions, such as skin ulcers to debilitation of internal organs, according to the study. These conditions are present in Asia, Africa, Americas, and Southern Europe.

Chagas disease is primarily located in Latin America and can cause intestinal and cardiac problems, which can lead to heart failure. Sleeping sickness is a deadly disease that affects both humans and animals, primarily in Africa.

In the study, researchers mapped the first class 1 FH enzyme, and discovered that the Leishmania major FH enzyme has a protein architecture that is different than the structure of human FH. They found that the Leishmania major FH enzyme has a structure whose appearance resembles a human heart.

“The fact that it is a novel fold does add to the idea that this is a good drug target,” Dr Drennan said. “It has a lot of potential.”

Researchers used tools that create crystals of proteins under anaerobic conditions. The researchers formed a crystal of the Leishmania major FH enzyme, and mapped out its structure for several months due to its complexity, according to the study.

Investigators believe that diseases can currently spread quickly in short timespans due to the nature of globalization. So, these diseases could potentially become widespread.

“I think it's important to reflect on these health issues, and more people in the US need to be aware of these diseases,” Dr Drennan concluded. “The world is getting to be a smaller place.”