9IVV
Crystal structure of human secretory glutaminyl cyclase in complex with the inhibitor 3-((2-(1H-imidazol-5-yl)ethyl)carbamoyl)-4-amino-1,2,5-oxadiazole 2-oxide (compound 13)
This is a non-PDB format compatible entry.
Summary for 9IVV
| Entry DOI | 10.2210/pdb9ivv/pdb |
| Descriptor | Glutaminyl-peptide cyclotransferase, ZINC ION, 4-azanyl-~{N}-[2-(1~{H}-imidazol-4-yl)ethyl]-2-oxidanidyl-1,2,5-oxadiazol-2-ium-3-carboxamide, ... (7 entities in total) |
| Functional Keywords | glutaminyl cyclase, inhibitor, complex, transferase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 38458.75 |
| Authors | Li, G.-B.,Yu, J.-L.,Zhou, C.,Ning, X.-L.,Mou, J.,Wu, J.-W.,Meng, F.-B. (deposition date: 2024-07-24, release date: 2025-03-12, Last modification date: 2025-03-19) |
| Primary citation | Yu, J.L.,Zhou, C.,Ning, X.L.,Mou, J.,Meng, F.B.,Wu, J.W.,Chen, Y.T.,Tang, B.D.,Liu, X.G.,Li, G.B. Knowledge-guided diffusion model for 3D ligand-pharmacophore mapping. Nat Commun, 16:2269-2269, 2025 Cited by PubMed Abstract: Pharmacophores are abstractions of essential chemical interaction patterns, holding an irreplaceable position in drug discovery. Despite the availability of many pharmacophore tools, the adoption of deep learning for pharmacophore-guided drug discovery remains relatively rare. We herein propose a knowledge-guided diffusion framework for 'on-the-fly' 3D ligand-pharmacophore mapping, named DiffPhore. It leverages ligand-pharmacophore matching knowledge to guide ligand conformation generation, meanwhile utilizing calibrated sampling to mitigate the exposure bias of the iterative conformation search process. By training on two self-established datasets of 3D ligand-pharmacophore pairs, DiffPhore achieves state-of-the-art performance in predicting ligand binding conformations, surpassing traditional pharmacophore tools and several advanced docking methods. It also manifests superior virtual screening power for lead discovery and target fishing. Using DiffPhore, we successfully identify structurally distinct inhibitors for human glutaminyl cyclases, and their binding modes are further validated through co-crystallographic analysis. We believe this work will advance the AI-enabled pharmacophore-guided drug discovery techniques. PubMed: 40050649DOI: 10.1038/s41467-025-57485-3 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.961 Å) |
Structure validation
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