6XZV
Structure of zVDR LBD-Calcitriol in complex with chimera 18
Summary for 6XZV
| Entry DOI | 10.2210/pdb6xzv/pdb |
| Descriptor | Vitamin D3 receptor A, URA-UIA-URL-URY-URV-UZN-LYS, 5-{2-[1-(5-HYDROXY-1,5-DIMETHYL-HEXYL)-7A-METHYL-OCTAHYDRO-INDEN-4-YLIDENE]-ETHYLIDENE}-4-METHYLENE-CYCLOHEXANE-1,3-DIOL, ... (4 entities in total) |
| Functional Keywords | nuclear receptor, foldamer, helix mimicry, protein-protein interaction, gene regulation |
| Biological source | Danio rerio (Zebrafish) More |
| Total number of polymer chains | 2 |
| Total formula weight | 35429.53 |
| Authors | Buratto, J.,Belorusova, A.Y.,Rochel, N.,Guichard, G. (deposition date: 2020-02-05, release date: 2021-02-17, Last modification date: 2024-01-24) |
| Primary citation | Cussol, L.,Mauran-Ambrosino, L.,Buratto, J.,Belorusova, A.Y.,Neuville, M.,Osz, J.,Fribourg, S.,Fremaux, J.,Dolain, C.,Goudreau, S.R.,Rochel, N.,Guichard, G. Structural Basis for alpha-Helix Mimicry and Inhibition of Protein-Protein Interactions with Oligourea Foldamers. Angew.Chem.Int.Ed.Engl., 60:2296-2303, 2021 Cited by PubMed Abstract: Efficient optimization of a peptide lead into a drug candidate frequently needs further transformation to augment properties such as bioavailability. Among the different options, foldamers, which are sequence-based oligomers with precise folded conformation, have emerged as a promising technology. We introduce oligourea foldamers to reduce the peptide character of inhibitors of protein-protein interactions (PPI). However, the precise design of such mimics is currently limited by the lack of structural information on how these foldamers adapt to protein surfaces. We report a collection of X-ray structures of peptide-oligourea hybrids in complex with ubiquitin ligase MDM2 and vitamin D receptor and show how such hybrid oligomers can be designed to bind with high affinity to protein targets. This work should enable the generation of more effective foldamer-based disruptors of PPIs in the context of peptide lead optimization. PubMed: 32935897DOI: 10.1002/anie.202008992 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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