8YTD
Crystal Structure of TrkA D5 domain in complex with two different macrocyclic peptides
Summary for 8YTD
| Entry DOI | 10.2210/pdb8ytd/pdb |
| Descriptor | High affinity nerve growth factor receptor, Macrocyclic Peptide, 1,2-ETHANEDIOL, ... (5 entities in total) |
| Functional Keywords | transferase |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 3 |
| Total formula weight | 15378.30 |
| Authors | Yamada, T.,Mihara, K.,Ueda, T.,Yamauchi, D.,Shimizu, M.,Ando, A.,Mayumi, K.,Nakata, Z.,Mikamiyama, H. (deposition date: 2024-03-25, release date: 2024-07-10, Last modification date: 2024-07-24) |
| Primary citation | Yamada, T.,Mihara, K.,Ueda, T.,Yamauchi, D.,Shimizu, M.,Ando, A.,Mayumi, K.,Nakata, Z.,Mikamiyama, H. Discovery and Hit to Lead Optimization of Macrocyclic Peptides as Novel Tropomyosin Receptor Kinase A Antagonists. J.Med.Chem., 67:11197-11208, 2024 Cited by PubMed Abstract: Tropomyosin receptor kinases (Trks) are receptor tyrosine kinases activated by neurotrophic factors, called neurotrophins. Among them, TrkA interacts with the nerve growth factor (NGF), which leads to pain induction. mRNA-display screening was carried out to discover a hit compound , which inhibits protein-protein interactions between TrkA and NGF. Subsequent structure optimization improving phosphorylation inhibitory activity and serum stability was pursued using a unique process that took advantage of the peptide being synthesized by translation from mRNA. This gave peptide , which showed an analgesic effect in a rat incisional pain model. The peptides described here can serve as a new class of analgesics, and the structure optimization methods reported provide a strategy for discovering new peptide drugs. PubMed: 38950284DOI: 10.1021/acs.jmedchem.4c00715 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.34 Å) |
Structure validation
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