3HY7

Crystal Structure of the Catalytic Domain of ADAMTS-5 in Complex with Marimastat

3HY7 の概要

• エントリーDOI: 10.2210/pdb3hy7/pdb
• 関連するPDBエントリー: 3B8Z 3HY9 3HYG
• 分子名称: A disintegrin and metalloproteinase with thrombospondin motifs 5, (2S,3R)-N~4~-[(1S)-2,2-dimethyl-1-(methylcarbamoyl)propyl]-N~1~,2-dihydroxy-3-(2-methylpropyl)butanediamide, ZINC ION, ... (5 entities in total)
• 機能のキーワード: alpha/beta structure, central five stranded beta-sheet, cleavage on pair of basic residues, disulfide bond, extracellular matrix, glycoprotein, hydrolase, metal-binding, metalloprotease, polymorphism, protease, secreted, zinc, zymogen
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted, extracellular space, extracellular matrix : Q9UNA0
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 49907.39

構造登録者

Shieh, H.-S.,Williams, J.M.,Caspers, N.,Mathis, K.J.,Tortorella, M.D.,Tomasselli, A. (登録日: 2009-06-22, 公開日: 2009-07-07, 最終更新日: 2024-11-06)

主引用文献

Tortorella, M.D.,Tomasselli, A.G.,Mathis, K.J.,Schnute, M.E.,Woodard, S.S.,Munie, G.,Williams, J.M.,Caspers, N.,Wittwer, A.J.,Malfait, A.M.,Shieh, H.S.
Structural and inhibition analysis reveals the mechanism of selectivity of a series of aggrecanase inhibitors
J.Biol.Chem., 284:24185-24191, 2009

PubMed Abstract: Several inhibitors of a series of cis-1(S)2(R)-amino-2-indanol-based compounds were reported to be selective for the aggrecanases, ADAMTS-4 and -5 over other metalloproteases. To understand the nature of this selectivity for aggrecanases, the inhibitors, along with the broad spectrum metalloprotease inhibitor marimastat, were independently bound to the catalytic domain of ADAMTS-5, and the corresponding crystal structures were determined. By comparing the structures, it was determined that the specificity of the relative inhibitors for ADAMTS-5 was not driven by a specific interaction, such as zinc chelation, hydrogen bonding, or charge interactions, but rather by subtle and indirect factors, such as water bridging, ring rigidity, pocket size, and shape, as well as protein conformation flexibility.

PubMed: 19586907
DOI: 10.1074/jbc.M109.029116

実験手法

X-RAY DIFFRACTION (1.69 Å)