5H3Q
Crystal Structure of TrkA kinase with ligand
Summary for 5H3Q
| Entry DOI | 10.2210/pdb5h3q/pdb |
| Descriptor | High affinity nerve growth factor receptor, 1-[(3S,4R)-4-[3,4-bis(fluoranyl)phenyl]-1-(2-methoxyethyl)pyrrolidin-3-yl]-3-(5-ethoxy-4-methyl-2-phenyl-pyrazol-3-yl)urea, 2,3-DIHYDROXY-1,4-DITHIOBUTANE, ... (5 entities in total) |
| Functional Keywords | trka inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 37325.97 |
| Authors | Noritaka, F. (deposition date: 2016-10-26, release date: 2017-02-22, Last modification date: 2024-11-13) |
| Primary citation | Furuya, N.,Momose, T.,Katsuno, K.,Fushimi, N.,Muranaka, H.,Handa, C.,Ozawa, T.,Kinoshita, T. The juxtamembrane region of TrkA kinase is critical for inhibitor selectivity Bioorg. Med. Chem. Lett., 27:1233-1236, 2017 Cited by PubMed Abstract: Although numerous crystal structures for protein kinases have been reported, many include only the kinase domain but not the juxtamembrane (JM) region, a critical activity-controlling segment of receptor tyrosine kinases (RTKs). In this study, we determined the X-ray crystal structure of the tropomyosin receptor kinase (Trk) A selective inhibitor A1 complexed with the TrkA kinase domain and the JM region. This structure revealed that the unique inhibitor-binding pocket created by a novel JM configuration yields significant potency and high selectivity against TrkB and TrkC. Moreover, we validated the importance of the JM region for the potency of A1 using in vitro assays. The introduction of moieties that interact with the JM region will be one of the most effective strategies for producing highly selective RTK inhibitors. PubMed: 28159414DOI: 10.1016/j.bmcl.2017.01.056 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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