6GFI
Structure of Human Mesotrypsin in complex with APPI variant T11V/M17R/I18F/F34V
Summary for 6GFI
| Entry DOI | 10.2210/pdb6gfi/pdb |
| Descriptor | PRSS3 protein, Amyloid-beta A4 protein, 1,2-ETHANEDIOL, ... (4 entities in total) |
| Functional Keywords | protein protein interactions, serine proteases, amyloid protein precursor inhibitor, protein binding |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 66947.03 |
| Authors | Shahar, A.,Cohen, I.,Radisky, E.,Papo, N.,Naftaly, S. (deposition date: 2018-04-30, release date: 2018-09-12, Last modification date: 2024-01-17) |
| Primary citation | Naftaly, S.,Cohen, I.,Shahar, A.,Hockla, A.,Radisky, E.S.,Papo, N. Mapping protein selectivity landscapes using multi-target selective screening and next-generation sequencing of combinatorial libraries. Nat Commun, 9:3935-3935, 2018 Cited by PubMed Abstract: Characterizing the binding selectivity landscape of interacting proteins is crucial both for elucidating the underlying mechanisms of their interaction and for developing selective inhibitors. However, current mapping methods are laborious and cannot provide a sufficiently comprehensive description of the landscape. Here, we introduce a novel and efficient strategy for comprehensively mapping the binding landscape of proteins using a combination of experimental multi-target selective library screening and in silico next-generation sequencing analysis. We map the binding landscape of a non-selective trypsin inhibitor, the amyloid protein precursor inhibitor (APPI), to each of the four human serine proteases (kallikrein-6, mesotrypsin, and anionic and cationic trypsins). We then use this map to dissect and improve the affinity and selectivity of APPI variants toward each of the four proteases. Our strategy can be used as a platform for the development of a new generation of target-selective probes and therapeutic agents based on selective protein-protein interactions. PubMed: 30258049DOI: 10.1038/s41467-018-06403-x PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
Download full validation report
