8D51
Parathyroid hormone 1 receptor extracellular domain complexed with a peptide ligand containing beta-3-homotryptophan
Summary for 8D51
| Entry DOI | 10.2210/pdb8d51/pdb |
| Descriptor | Parathyroid hormone/parathyroid hormone-related peptide receptor, PTHrP[1-36], 1,2-ETHANEDIOL, ... (5 entities in total) |
| Functional Keywords | parathyroid hormone 1 receptor, signaling, beta-amino acid, signaling protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 14945.42 |
| Authors | Yu, Z.,Kreitler, D.F.,Gellman, S.H. (deposition date: 2022-06-03, release date: 2023-06-14, Last modification date: 2023-12-27) |
| Primary citation | Yu, Z.,Kreitler, D.F.,Chiu, Y.T.T.,Xu, R.,Bruchs, A.T.,Bingman, C.A.,Gellman, S.H. Harnessing Aromatic-Histidine Interactions through Synergistic Backbone Extension and Side Chain Modification. Angew.Chem.Int.Ed.Engl., 62:e202308100-e202308100, 2023 Cited by PubMed Abstract: Peptide engineering efforts have delivered drugs for diverse human diseases. Side chain alteration is among the most common approaches to designing new peptides for specific applications. The peptide backbone can be modified as well, but this strategy has received relatively little attention. Here we show that new and favorable contacts between a His side chain on a target protein and an aromatic side chain on a synthetic peptide ligand can be engineered by rational and coordinated side chain modification and backbone extension. Side chain modification alone was unsuccessful. Binding measurements, high-resolution structural studies and pharmacological outcomes all support the synergy between backbone and side chain modification in engineered ligands of the parathyroid hormone receptor-1, which is targeted by osteoporosis drugs. These results should motivate other structure-based designs featuring coordinated side chain modification and backbone extension to enhance the engagement of peptide ligands with target proteins. PubMed: 37587780DOI: 10.1002/anie.202308100 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
Download full validation report
