3EDZ

Crystal structure of catalytic domain of TACE with hydroxamate inhibitor

3EDZ の概要

• エントリーDOI: 10.2210/pdb3edz/pdb
• 関連するPDBエントリー: 1BKC 2fv5 2fv9
• 関連するBIRD辞書のPRD_ID: PRD_000919
• 分子名称: ADAM 17, ZINC ION, N-{(2R)-2-[2-(hydroxyamino)-2-oxoethyl]-4-methylpentanoyl}-3-methyl-L-valyl-N-(2-aminoethyl)-L-alaninamide, ... (6 entities in total)
• 機能のキーワード: hydrolase, zn-endopeptidase, cleavage on pair of basic residues, glycoprotein, membrane, metal-binding, metalloprotease, notch signaling pathway, phosphoprotein, protease, sh3-binding, transmembrane, zymogen
• 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: 62687.58

構造登録者

Mazzola, R.D.,Zhu, Z.,Sinning, L.,McKittrick, B.,Lavey, B.,Spitler, J.,Kozlowski, J.,Neng-Yang, S.,Zhou, G.,Guo, Z.,Orth, P.,Madison, V.,Sun, J.,Lundell, D.,Niu, X. (登録日: 2008-09-03, 公開日: 2008-09-23, 最終更新日: 2024-10-30)

主引用文献

Mazzola, R.D.,Zhu, Z.,Sinning, L.,McKittrick, B.,Lavey, B.,Spitler, J.,Kozlowski, J.,Neng-Yang, S.,Zhou, G.,Guo, Z.,Orth, P.,Madison, V.,Sun, J.,Lundell, D.,Niu, X.
Discovery of novel hydroxamates as highly potent tumor necrosis factor-alpha converting enzyme inhibitors. Part II: optimization of the S3' pocket.
Bioorg.Med.Chem.Lett., 18:5809-5814, 2008

PubMed Abstract: A series of cyclopropyl hydroxamic acids were prepared. Many of the compounds displayed picomolar affinity for the TACE enzyme while maintaining good to excellent selectivity profiles versus MMP-1, -2, -3, -7, -14, and ADAM-10. X-ray analysis of an inhibitor in the TACE active site indicated that the molecules bound to the enzyme in the S1'-S3' pocket.

PubMed: 18835710
DOI: 10.1016/j.bmcl.2008.09.045

実験手法

X-RAY DIFFRACTION (1.9 Å)