ArticleScientific reports2014
Identification of essential histidine residues involved in heme binding and Hemozoin formation in heme detoxification protein from Plasmodium falciparum.
Article in Scientific reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 32 citations in OpenAlex.
- The Plasmodium heme detoxification protein functions in mitochondrial protein synthesis.Nature communications · 2026Article
- Hemoglobin Digestion Genes Are Conserved in Lizard-InfectiveEcology and evolution · 2026Article
- Potential of Enzymatically Synthesized Hemozoin Analog as Th1 Cell Adjuvant.Nanomaterials (Basel, Switzerland) · 2024Article
- Cryo-tomography and 3D Electron Diffraction Reveal the Polar Habit and Chiral Structure of the Malaria Pigment Crystal Hemozoin.ACS central science · 2024Article
- Uncovering the Absolute Structure of the Malarial Pigment Crystal, Hemozoin, Using Cryo-electron Tomography and Three-Dimensional Electron Diffraction.ACS central science · 2024Article
- α-Glucosidase isoform G contributes to heme detoxification inCurrent research in insect science · 2024Article
- In Vitro and In Silico Antimalarial Evaluation of FM-AZ, a New Artemisinin Derivative.Medicines (Basel, Switzerland) · 2022Article
- Malaria Pigment Crystals: The Achilles' Heel of the Malaria Parasite.ChemMedChem · 2021Review
- Potent Antimalarial Activity of Two Arenes Linked with Triamine Designed To Have Multiple Interactions with Heme.ACS medicinal chemistry letters · 2018Article
- Prediction Model for Antimalarial Activities of Hemozoin Inhibitors by Using Physicochemical Properties.Antimicrobial agents and chemotherapy · 2018Article
- A novel blood-feeding detoxification pathway in Nippostrongylus brasiliensis L3 reveals a potential checkpoint for arresting hookworm development.PLoS pathogens · 2018Article
- In Silico Knockout Screening ofBioMed research international · 2018Article
- Unraveling heme detoxification in the malaria parasite by in situ correlative X-ray fluorescence microscopy and soft X-ray tomography.Scientific reports · 2017Article
- Biochemistry of malaria parasite infected red blood cells by X-ray microscopy.Scientific reports · 2017Article
- High-Throughput Screening and Prediction Model Building for Novel Hemozoin Inhibitors Using Physicochemical Properties.Antimicrobial agents and chemotherapy · 2017Article
- Comparative genome-wide analysis and evolutionary history of haemoglobin-processing and haem detoxification enzymes in malarial parasites.Malaria journal · 2016Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Malaria parasites digest hemoglobin within a food vacuole to supply amino acids, releasing the toxic product heme. During the detoxification, toxic free heme is converted into an insoluble crystalline form called hemozoin (Hz). Heme detoxification protein (HDP) in Plasmodium falciparum is one of the most potent of the hemozoin-producing enzymes. However, the reaction mechanisms of HDP are poorly understood. We identified the active site residues in HDP using a combination of Hz formation assay and spectroscopic characterization of mutant proteins. Replacement of the critical histidine residues His122, His172, His175, and His197 resulted in a reduction in the Hz formation activity to approximately 50% of the wild-type protein. Spectroscopic characterization of histidine-substituted mutants revealed that His122 binds heme and that His172 and His175 form a part of another heme-binding site. Our results show that the histidine residues could be present in the individual active sites and could be ligated to each heme. The interaction between heme and the histidine residues would serve as a molecular tether, allowing the proper positioning of two hemes to enable heme dimer formation. The heme dimer would act as a seed for the crystal growth of Hz in P. falciparum.
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