9F6H
Crystal structure of bovine alpha-chymotrypsin in complex with the bicyclic peptide inhibitor MP5.4.3
Summary for 9F6H
| Entry DOI | 10.2210/pdb9f6h/pdb |
| Descriptor | Chymotrypsin A chain A, Chymotrypsin A chain B, Chymotrypsin A chain C, ... (5 entities in total) |
| Functional Keywords | serine protease; bicyclic peptide, hydrolase |
| Biological source | Bos taurus (cattle) More |
| Total number of polymer chains | 4 |
| Total formula weight | 26707.31 |
| Authors | Vascon, F.,Mazzocato, Y.,Trevisan, L.,Linciano, S.,Romanyuk, Z.,Angelini, A.,Cendron, L. (deposition date: 2024-05-01, release date: 2025-05-28, Last modification date: 2025-07-09) |
| Primary citation | Linciano, S.,Mazzocato, Y.,Romanyuk, Z.,Vascon, F.,Farrera-Soler, L.,Will, E.,Xing, Y.,Chen, S.,Kumada, Y.,Simeoni, M.,Scarso, A.,Cendron, L.,Heinis, C.,Angelini, A. Screening macrocyclic peptide libraries by yeast display allows control of selection process and affinity ranking. Nat Commun, 16:5367-5367, 2025 Cited by PubMed Abstract: Macrocyclic peptides represent an attractive drug modality due to their favourable properties and amenability to in vitro evolution techniques such as phage or mRNA display. Although very powerful, these technologies are not without limitations. In this work, we address some of their drawbacks by developing a yeast display-based strategy to generate, screen and characterise structurally diverse disulfide-cyclised peptides. The use of quantitative flow cytometry enables real-time monitoring of the screening of millions of individual macrocyclic peptides, leading to the identification of ligands with good binding properties to five different protein targets. X-ray analysis of a selected ligand in complex with its target reveals optimal shape complementarity and extensive surface interaction, explaining its exquisite affinity and selectivity. The yeast display-based approach described here offers a facile, quantitative and cost-effective alternative to rapidly and efficiently discover and characterise genetically encoded macrocyclic peptide ligands with sufficiently good binding properties against therapeutically relevant targets. PubMed: 40562762DOI: 10.1038/s41467-025-60907-x PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.42 Å) |
Structure validation
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