Scientific Publications by FDA Staff
PLoS Pathog 2008 Apr 25;4(4):e1000053
HDP-a novel heme detoxification protein from the malaria parasite.
Jani D, Nagarkatti R, Beatty W, Angel R, Slebodnick C, Andersen J, Kumar S, Rathore D
Jani, D (reprint author), Virginia Tech, Virgina Bioinformat Inst, Blacksburg, VA USA Virginia Tech, Virgina Bioinformat Inst, Blacksburg, VA USA Washington Univ, Sch Med, St Louis, MO USA Virginia Tech, Dept Geosci, Blacksburg, VA USA Virginia Tech, Dept Chem, Blacksburg, VA USA Natl Inst Hlth, Lab Malaria & Vector Res, Rockville, MD USA US FDA, Bethesda, MD 20014 USA
When malaria parasites infect host red blood cells (RBC) and proteolyze hemoglobin, a unique, albeit poorly understood parasite-specific mechanism, detoxifies released heme into hemozoin (Hz). Here, we report the identification and characterization of a novel Plasmodium Heme Detoxification Protein (HDP) that is extremely potent in converting heme into Hz. HDP is functionally conserved across Plasmodium genus and its gene locus could not be disrupted. Once expressed, the parasite utilizes a circuitous "Outbound-Inbound" trafficking route by initially secreting HDP into the cytosol of infected RBC. A subsequent endocytosis of host cytosol (and hemoglobin) delivers HDP to the food vacuole (FV), the site of Hz formation. As Hz formation is critical for survival, involvement of HDP in this process suggests that it could be a malaria drug target.
|Category: Journal Article|
|PubMed ID: #18437218|
|Includes FDA Authors from Scientific Area(s): Biologics|
|Entry Created: 2011-10-04||Entry Last Modified: 2012-08-29|