2RJP

Crystal structure of ADAMTS4 with inhibitor bound

2RJP の概要

• エントリーDOI: 10.2210/pdb2rjp/pdb
• 関連するPDBエントリー: 2RJQ 3B2Z
• 分子名称: ADAMTS-4, ZINC ION, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: metalloprotease domain, aggrecanase, cleavage on pair of basic residues, extracellular matrix, glycoprotein, hydrolase, metal-binding, polymorphism, secreted, zinc, zymogen
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted, extracellular space, extracellular matrix (By similarity): O75173
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 139667.67

構造登録者

Mosyak, L.,Stahl, M.,Somers, W. (登録日: 2007-10-15, 公開日: 2007-12-11, 最終更新日: 2024-11-06)

主引用文献

Mosyak, L.,Georgiadis, K.,Shane, T.,Svenson, K.,Hebert, T.,McDonagh, T.,Mackie, S.,Olland, S.,Lin, L.,Zhong, X.,Kriz, R.,Reifenberg, E.L.,Collins-Racie, L.A.,Corcoran, C.,Freeman, B.,Zollner, R.,Marvell, T.,Vera, M.,Sum, P.E.,Lavallie, E.R.,Stahl, M.,Somers, W.
Crystal structures of the two major aggrecan degrading enzymes, ADAMTS4 and ADAMTS5.
Protein Sci., 17:16-21, 2008

PubMed Abstract: Aggrecanases are now believed to be the principal proteinases responsible for aggrecan degradation in osteoarthritis. Given their potential as a drug target, we solved crystal structures of the two most active human aggrecanase isoforms, ADAMTS4 and ADAMTS5, each in complex with bound inhibitor and one wherein the enzyme is in apo form. These structures show that the unliganded and inhibitor-bound enzymes exhibit two essentially different catalytic-site configurations: an autoinhibited, nonbinding, closed form and an open, binding form. On this basis, we propose that mature aggrecanases exist as an ensemble of at least two isomers, only one of which is proteolytically active.

PubMed: 18042673
DOI: 10.1110/ps.073287008

実験手法

X-RAY DIFFRACTION (2.8 Å)