TUESDAY, JUNE 19, 2018

Small antibodies suggest vulnerability in parasites that cause diseases

Small antibodies suggest vulnerability in parasites that cause diseases.
Small antibodies suggest vulnerability in parasites that cause diseases. | Courtesy of biology.usf.edu
Scientists from Whitehead Institute have found a potential target for drugs that could stop parasites from entering host cells thanks to an enzyme that is important to the parasite’s infectious behavior, especially for malaria and toxoplasmosis.

These enzymes are known as kinases.

"This work reveals something interesting about this class of enzymes," Whitehead Fellow Sebastian Lourido said. "It's the first time a calcium-regulated kinase has been shown to be activated in this manner. The principle that we identify is really important: we've found a new vulnerability within an enzyme that we know is extremely important to this class of parasites -- including Plasmodium, the parasite that causes malaria -- and is absent from humans."

Kinases monitor the activity of Toxoplasma gondii, which causes toxoplasmosis. One specific nanobody, 1B7, steadies CDPK1 to conform with the structure of the kinases and nanobodies.

"The location where 1B7 binds to CDPK1 is a new drug target that people had not considered before," Jessica Ingram, a postdoctoral researcher in Ploegh's lab and one of the lead authors of the PNAS paper, said. "We'd like to do some drug screens in the presence of the nanobody to see if we can find small molecules that bind in the same way. We could also look at other nanobodies against other kinases to see if this is applicable to other parasites and systems."

Toxoplasmosis results in diseases within specific individuals who have compromised immune systems, infants, and pregnant women. This parasite is closely linked to the parasite that causes malaria, Plasmodium. Researching Toxoplasmosis can help researchers better understand the way malaria infects the body and spreads.

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Whitehead Institute

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