8PI3
Cathepsin S Y132D mutant in complex with NNPI-C10 inhibitor
This is a non-PDB format compatible entry.
Summary for 8PI3
| Entry DOI | 10.2210/pdb8pi3/pdb |
| Related | 8RND |
| Descriptor | Cathepsin S, NNPI-C10 inhibitor, CHLORIDE ION, ... (9 entities in total) |
| Functional Keywords | protease, inhibitor, complex, cathepsin, oncoprotein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 28021.71 |
| Authors | Petruzzella, A.,Lau, K.,Pojer, F.,Oricchio, E. (deposition date: 2023-06-21, release date: 2024-06-05, Last modification date: 2024-09-11) |
| Primary citation | Petruzzella, A.,Bruand, M.,Santamaria-Martinez, A.,Katanayeva, N.,Reymond, L.,Wehrle, S.,Georgeon, S.,Inel, D.,van Dalen, F.J.,Viertl, D.,Lau, K.,Pojer, F.,Schottelius, M.,Zoete, V.,Verdoes, M.,Arber, C.,Correia, B.E.,Oricchio, E. Antibody-peptide conjugates deliver covalent inhibitors blocking oncogenic cathepsins. Nat.Chem.Biol., 20:1188-1198, 2024 Cited by PubMed Abstract: Cysteine cathepsins are a family of proteases that are relevant therapeutic targets for the treatment of different cancers and other diseases. However, no clinically approved drugs for these proteins exist, as their systemic inhibition can induce deleterious side effects. To address this problem, we developed a modular antibody-based platform for targeted drug delivery by conjugating non-natural peptide inhibitors (NNPIs) to antibodies. NNPIs were functionalized with reactive warheads for covalent inhibition, optimized with deep saturation mutagenesis and conjugated to antibodies to enable cell-type-specific delivery. Our antibody-peptide inhibitor conjugates specifically blocked the activity of cathepsins in different cancer cells, as well as osteoclasts, and showed therapeutic efficacy in vitro and in vivo. Overall, our approach allows for the rapid design of selective cathepsin inhibitors and can be generalized to inhibit a broad class of proteases in cancer and other diseases. PubMed: 38811854DOI: 10.1038/s41589-024-01627-z PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.73 Å) |
Structure validation
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