5H3Q

Crystal Structure of TrkA kinase with ligand

5H3Q の概要

• エントリーDOI: 10.2210/pdb5h3q/pdb
• 分子名称: 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)
• 機能のキーワード: trka inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 37325.97

構造登録者

Noritaka, F. (登録日: 2016-10-26, 公開日: 2017-02-22, 最終更新日: 2024-11-13)

主引用文献

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

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: 28159414
DOI: 10.1016/j.bmcl.2017.01.056

実験手法

X-RAY DIFFRACTION (2.1 Å)