Heme Detoxification Protein (HDP)is a unique protein contained in the malaria genome and it provides a feasible target for development of anti-malaria drugs, researchers at the Virginia Bioinformatics Institute (VBI) at Virginia Tech have reported.
They have characterized HDP and demonstrated that it plays a major role in protecting Plasmodium as the pathogen pursues infection of its host.
The Plasmodium parasite, which is responsible for causing malaria in humans is transmitted through the bites of infected mosquitoes. Once inside the human body, the parasite initially develops in the liver and later, upon release, infects red blood cells.
After a host of red blood cells get infected, a rapid growth ensues, supported by the parasite's consumption of hemoglobin, the oxygen-transporting protein that constitutes a massive 90 percent of the total protein present inside each red blood cell.
Destruction on this scale releases large quantities of heme, the prosthetic group responsible for oxygen transport in hemoglobin.
Free heme is highly dangerous and to protect itself from this toxic onslaught, the parasite uses a novel mechanism where it rapidly converts heme into a crystalline material known as hemozoin.
"We discovered HDP as part of a functional genomics initiative that is focused on the identification of malaria proteins involved in disease pathology. A combination of cellular and biochemical approaches allowed us to rigorously characterize HDP," said Dr. Dharmendar Rathore, Assistant Professor at VBI.
"It appears that HDP has a number of striking features that make it a promising candidate as a drug target. HDP is not only capable of rapidly converting heme into its non-toxic counterpart hemozoin, but it is highly conserved in all the species of the parasite and also appears to be critical for its survival."
"The beauty of this discovery is that, while HDP has robust interactions with heme, it lacks homology to any of the known heme-binding proteins and has therefore eluded detection during previous attempts by several groups to identify parasite factors responsible for hemozoin formation," he added.
The findings are published in the open-access journal PLoS Pathogens.