9FZV
Structure of cathepsin B1 from Schistosoma mansoni (SmCB1) in complex with a carborane inhibitor
This is a non-PDB format compatible entry.
Summary for 9FZV
| Entry DOI | 10.2210/pdb9fzv/pdb |
| Related | 3QSD 3S3Q 3S3R 4I04 4I05 4I07 5OGQ 5OGR 8CC2 8CCU 8CD9 |
| Descriptor | Cathepsin B-like peptidase (C01 family), carborane inhibitor, 1,2-ETHANEDIOL, ... (4 entities in total) |
| Functional Keywords | protease, parasite, inhibitor, carborane, hydrolase |
| Biological source | Schistosoma mansoni |
| Total number of polymer chains | 3 |
| Total formula weight | 87245.00 |
| Authors | Jilkova, A.,Fanfrlik, J.,Brynda, J.,Spiwokova, P.,Horn, M.,Holub, J.,Guetschow, M.,Mares, M. (deposition date: 2024-07-06, release date: 2025-10-29, Last modification date: 2026-01-28) |
| Primary citation | Holub, J.,Jilkova, A.,Lemke, C.,Cianni, L.,Spiwokova, P.,Horn, M.,Breuer, C.,Leontovyc, A.,Brynda, J.,Mertlikova-Kaiserova, H.,Chanova, M.,Dos Reis Rocho, F.,Montanari, C.A.,El-Sakkary, N.,Caffrey, C.R.,Gutschow, M.,Hnyk, D.,Mares, M.,Fanfrlik, J. Fat or flat? The impact of dipole moment vectors on non-covalent interactions between aromatic tags and macromolecules. Inorg Chem Front, 13:364-376, 2026 Cited by PubMed Abstract: The -1,2-CBH carborane is a recognized 3D aromatic icosahedral building block, with an electron distribution governed by the outer hydridic BH and acidic CH vertices. We attached the carborane cage to a peptidomimetic scaffold to generate an active-site inhibitor of SmCB1, a protease drug target in the Schistosoma pathogen. The carborane-tagged compound exhibited superior inhibitor affinity and bioactivity compared to its conventional 2D aromatic phenyl analog. Quantum mechanical computations, based on the crystal structure of the protease-inhibitor complex, revealed that the carborane tag contributed to inhibitor binding not only through nonpolar interactions but also a key hydrogen bond between its CH vertex and a negatively charged residue in the binding site. This interaction, driven by the large dipole moment of the carborane cage, resulted in a more favorable energy contribution than that of the phenyl group in the 2D analog. The carborane pharmacophore boosted affinity for SmCB1 and conferred specific anti-schistosomal activity, highlighting its potential in protein ligand design. PubMed: 41127420DOI: 10.1039/d5qi01546d PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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