9voa

Fasciola hepatica calcium binding protein FhCaBP4

spinqualitylabelsall models 9voa, resolution 1.93Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9voa is a 2 chain structure with sequence from Fasciola hepatica. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.93Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function I6U578_FASHE Publication Abstract from PubMed Fasciola hepatica remains a global health and economic concern, and treatment still relies heavily on triclabendazole. At the parasite-host interface, F. hepatica calcium-binding proteins (FhCaBPs) have a unique EF-hand/DLC-like domain fusion found only in trematodes. This makes it a parasite-specific target for small compounds and vaccinations. To enable novel therapeutic strategies, we report the first elevated-resolution structure of a full-length FhCaBP4. The apo structure was determined at 1.93 A resolution, revealing a homodimer architecture that integrates an N-terminal, calmodulin-like, EF-hand pair with a C-terminal dynein light chain (DLC)-like domain. Structure-guided in silico mutagenesis identified a flexible, 16-residue beta4-beta5 loop (LTGSYWMKFSHEPFMS) with an FSHEPF core that demonstrates greater energetic variability than its FhCaBP2 counterpart, likely explaining the distinct ligand-binding profiles of these paralogs. Molecular dynamics simulations and AlphaFold3 modeling suggest that EF-hand 2 acts as the primary calcium-binding site, with calcium coordination inducing partial rigidification and modest expansion of the protein structure. Microscale thermophoresis confirmed calcium as the major ligand, while calmodulin antagonists bound with lower affinity and praziquantel demonstrated no interaction. Thermal shift assays revealed calcium-dependent stabilization and a merger of biphasic unfolding transitions. These results suggest that FhCaBP4 functions as a calcium-responsive signaling hub, with an allosterically coupled EF-hand-DLC interface that could serve as a structurally tractable platform for drug targeting in trematodes. Structural Insights and Calcium-Switching Mechanism of Fasciola hepatica Calcium-Binding Protein FhCaBP4.,Shin B, Park S, Park I, Shin H, Bang K, Kim S, Hwang KY Int J Mol Sci. 2025 Aug 5;26(15):7584. doi: 10.3390/ijms26157584. PMID:40806711 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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