3LEA

Crystal structure of the catalytic domain of TACE with Isoindolinone-biphenyl-hydantoin inhibitor

3LEA の概要

• エントリーDOI: 10.2210/pdb3lea/pdb
• 関連するPDBエントリー: 1bkc 3L0T 3L0V 3LE9
• 分子名称: Disintegrin and metalloproteinase domain-containing protein 17, 2-{[(4R)-2,5-dioxo-4-(4-pyridin-3-ylphenyl)imidazolidin-4-yl]methyl}-6-methoxy-1-oxo-1H-isoindolium, ZINC ION, ... (5 entities in total)
• 機能のキーワード: glycoprotein, membrane, metal-binding, metalloprotease, notch signaling pathway, phosphoprotein, protease, transmembrane, zymogen, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P78536
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 62184.05

構造登録者

Orth, P. (登録日: 2010-01-14, 公開日: 2010-12-08, 最終更新日: 2024-11-20)

主引用文献

Yu, W.,Tong, L.,Kim, S.H.,Wong, M.K.,Chen, L.,Yang, D.Y.,Shankar, B.B.,Lavey, B.J.,Zhou, G.,Kosinski, A.,Rizvi, R.,Li, D.,Feltz, R.J.,Piwinski, J.J.,Rosner, K.E.,Shih, N.Y.,Siddiqui, M.A.,Guo, Z.,Orth, P.,Shah, H.,Sun, J.,Umland, S.,Lundell, D.J.,Niu, X.,Kozlowski, J.A.
Biaryl substituted hydantoin compounds as TACE inhibitors.
Bioorg.Med.Chem.Lett., 20:5286-5289, 2010

PubMed Abstract: We disclose further optimization of hydantoin TNF-alpha convertase enzyme (TACE) inhibitors. SAR with respect to the non-prime region of TACE active site was explored. A series of biaryl substituted hydantoin compounds was shown to have sub-nanomolar K(i), good rat PK, and good selectivity versus MMP-1, -2, -3, -7, -9, and -13.

PubMed: 20663669
DOI: 10.1016/j.bmcl.2010.06.134

実験手法

X-RAY DIFFRACTION (2 Å)