Schistosoma mansoni cathepsin D1 (SmCD1) has been shown to be an essential enzyme for helminth metabolism due to its role in haemoglobin degradation: a key amino-acid source for the developing parasite. Therefore, the enzyme is a potential target for the development of antischistosomal inhibitors. SmCD1 has significant sequence identity to cathepsin D-like proteases found in other schistosome species and homology to mammalian aspartic proteases. Here, we report the first crystal structures of a helminth cathepsin D, SmCD1, and have identified a single-domain antibody (nanobody) that specifically binds to SmCD1 with nanomolar affinity but does not recognize human cathepsin D. We have mapped the epitope of the nanobody by determining the crystal structure of the enzyme-nanobody complex, revealing the conformation of SmCD1 in the propeptide-bound state.
Journal article
2026-02-01T00:00:00+00:00
82
140 - 150
10
Schistosoma mansoni, X-ray crystallography, cathepsin D, nanobodies, Schistosoma mansoni, Cathepsin D, Animals, Crystallography, X-Ray, Single-Domain Antibodies, Protein Conformation, Models, Molecular, Humans, Amino Acid Sequence, Helminth Proteins