ArticleJournal of molecular biology2009
Crystal structures of the histo-aspartic protease (HAP) from Plasmodium falciparum.
Article in Journal of molecular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 57 citations in OpenAlex.
- Unlocking the Enigmas ofCurrent pharmaceutical design · 2026Article
- Aspartyl protease inhibition interferes with Plasmodium falciparum asexual blood-stage and early gametocyte development.Malaria journal · 2025Article
- Post-Translational Modifications of Proteins of Malaria Parasites during the Life Cycle.International journal of molecular sciences · 2024Review
- Evaluation of antiplasmodial activity in silico and in vitro of N-acylhydrazone derivatives.BMC chemistry · 2022Article
- Methods Used to Investigate theFrontiers in cellular and infection microbiology · 2021Review
- Activation mechanism of plasmepsins, pepsin-like aspartic proteases from Plasmodium, follows a unique trans-activation pathway.The FEBS journal · 2021Article
- Malaria parasite plasmepsins: More than just plain old degradative pepsins.The Journal of biological chemistry · 2020Review
- FAM105A/OTULINL Is a Pseudodeubiquitinase of the OTU-Class that Localizes to the ER Membrane.Structure (London, England : 1993) · 2019Article
- Overexpression of plasmepsin II and plasmepsin III does not directly cause reduction in Plasmodium falciparum sensitivity to artesunate, chloroquine and piperaquine.International journal for parasitology. Drugs and drug resistance · 2019Article
- Deciphering the mechanism of potent peptidomimetic inhibitors targeting plasmepsins - biochemical and structural insights.The FEBS journal · 2018Article
- A Perspective on Thiazolidinone Scaffold Development as a New Therapeutic Strategy for Toxoplasmosis.Frontiers in cellular and infection microbiology · 2018Article
- The Potential of Secondary Metabolites from Plants as Drugs or Leads against Protozoan Neglected Diseases-Part III: In-Silico Molecular Docking Investigations.Molecules (Basel, Switzerland) · 2016Review
- Understanding the structural basis of substrate recognition by Plasmodium falciparum plasmepsin V to aid in the design of potent inhibitors.Scientific reports · 2016Article
- Comparative genome-wide analysis and evolutionary history of haemoglobin-processing and haem detoxification enzymes in malarial parasites.Malaria journal · 2016Article
- Enzymatic Characterization of Recombinant Food Vacuole Plasmepsin 4 from the Rodent Malaria Parasite Plasmodium berghei.PloS one · 2015Article
- Article
- Crystal structure of a putative aspartic proteinase domain of the Mycobacterium tuberculosis cell surface antigen PE_PGRS16.FEBS open bio · 2013Article
- Recent advances in plasmepsin medicinal chemistry and implications for future antimalarial drug discovery efforts.Current topics in medicinal chemistry · 2012Review
- Structural studies of vacuolar plasmepsins.Biochimica et biophysica acta · 2012Review
- Structural insights into the activation and inhibition of histo-aspartic protease from Plasmodium falciparum.Biochemistry · 2011Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
The structures of recombinant histo-aspartic protease (HAP) from malaria-causing parasite Plasmodium falciparum as apoenzyme and in complex with two inhibitors, pepstatin A and KNI-10006, were solved at 2.5-, 3.3-, and 3.05-A resolutions, respectively. In the apoenzyme crystals, HAP forms a tight dimer not seen previously in any aspartic protease. The interactions between the monomers affect the conformation of two flexible loops, the functionally important "flap" (residues 70-83) and its structural equivalent in the C-terminal domain (residues 238-245), as well as the orientation of helix 225-235. The flap is found in an open conformation in the apoenzyme. Unexpectedly, the active site of the apoenzyme contains a zinc ion tightly bound to His32 and Asp215 from one monomer and to Glu278A from the other monomer, with the coordination of Zn resembling that seen in metalloproteases. The flap is closed in the structure of the pepstatin A complex, whereas it is open in the complex with KNI-10006. Although the binding mode of pepstatin A is significantly different from that in other pepsin-like aspartic proteases, its location in the active site makes unlikely the previously proposed hypothesis that HAP is a serine protease. The binding mode of KNI-10006 is unusual compared with the binding of other inhibitors from the KNI series to aspartic proteases. The novel features of the HAP active site could facilitate design of specific inhibitors used in the development of antimalarial drugs.
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