ArticleMolecular and biochemical parasitology2011
Biochemical characterization of Plasmodium falciparum dipeptidyl aminopeptidase 1.
Article in Molecular and biochemical parasitology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 44 citations in OpenAlex.
- Gain-of-function PfAAT1 mutations compensate for impaired PfCRT function inResearch square · 2026Article
- Structure-based discovery of Plasmodium falciparum DPAP-1 inhibitor and its experimental validation as an antimalarial agent.Folia microbiologica · 2026Article
- Heme processing in the malaria parasite, Plasmodium falciparum: a time-dependent basal-level analysis.Communications biology · 2025Article
- Evolutionary Analysis of Dipeptidyl Peptidase I.International journal of molecular sciences · 2022Article
- Characterization of P. falciparum dipeptidyl aminopeptidase 3 specificity identifies differences in amino acid preferences between peptide-based substrates and covalent inhibitors.The FEBS journal · 2019Article
- Biguanide is a modifiable pharmacophore for recruitment of endogenous ZnBiometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2019Review
- Identification of Plasmodium dipeptidyl aminopeptidase allosteric inhibitors by high throughput screening.PloS one · 2019Article
- Evidence for Regulation of Hemoglobin Metabolism and Intracellular Ionic Flux by the Plasmodium falciparum Chloroquine Resistance Transporter.Scientific reports · 2018Article
- Plasmodium falciparum dipeptidyl aminopeptidase 3 activity is important for efficient erythrocyte invasion by the malaria parasite.PLoS pathogens · 2018Article
- Using in Vitro Evolution and Whole Genome Analysis To Discover Next Generation Targets for Antimalarial Drug Discovery.ACS infectious diseases · 2018Review
- Mapping the malaria parasite druggable genome by using in vitro evolution and chemogenomics.Science (New York, N.Y.) · 2018Article
- Proteases as antimalarial targets: strategies for genetic, chemical, and therapeutic validation.The FEBS journal · 2017Review
- Identification, immunolocalization, and characterization analyses of an exopeptidase of papain superfamily, (cathepsin C) from Clonorchis sinensis.Parasitology research · 2014Article
- Unnatural amino acids increase activity and specificity of synthetic substrates for human and malarial cathepsin C.Amino acids · 2014Article
- A proteolytic cascade controls lysosome rupture and necrotic cell death mediated by lysosome-destabilizing adjuvants.PloS one · 2014Article
- The antimalarial natural product symplostatin 4 is a nanomolar inhibitor of the food vacuole falcipains.Chemistry & biology · 2012Article
- Proteases as regulators of pathogenesis: examples from the Apicomplexa.Biochimica et biophysica acta · 2012Review
- Article
- Detection of protease activities by flash chronopotentiometry using a reversible polycation-sensitive polymeric membrane electrode.Analytical biochemistry · 2011Article
- Proteases in malaria parasites - a phylogenomic perspective.Current genomics · 2011Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Dipeptidyl aminopeptidase 1 (DPAP1) is an essential food vacuole enzyme with a putative role in hemoglobin catabolism by the erythrocytic malaria parasite. Here, the biochemical properties of DPAP1 have been investigated and compared to those of the human ortholog cathepsin C. To facilitate the characterization of DPAP1, we have developed a method for the production of purified recombinant DPAP1 with properties closely resembling those of the native enzyme. Like cathepsin C, DPAP1 is a chloride-activated enzyme that is most efficient in catalyzing amide bond hydrolysis at acidic pH values. The monomeric quaternary structure of DPAP1 differs from the homotetrameric structure of cathepsin C, which suggests that tetramerization is required for a cathepsin C-specific function. The S1 and S2 subsite preferences of DPAP1 and cathepsin C were profiled with a positional scanning synthetic combinatorial library. The S1 preferences bore close similarity to those of other C1-family cysteine peptidases. The S2 subsites of both DPAP1 and cathepsin C accepted aliphatic hydrophobic residues, proline, and some polar residues, yielding a distinct specificity profile. DPAP1 efficiently catalyzed the hydrolysis of several fluorogenic dipeptide substrates; surprisingly, however, a potential substrate with a P2-phenylalanine residue was instead a competitive inhibitor. Together, our biochemical data suggest that DPAP1 accelerates the production of amino acids from hemoglobin by bridging the gap between the endopeptidase and aminopeptidase activities of the food vacuole. Two reversible cathepsin C inhibitors potently inhibited both recombinant and native DPAP1, thereby validating the use of recombinant DPAP1 for future inhibitor discovery and characterization.
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