4JQG

Crystal structure of an inactive mutant of MMP-9 catalytic domain in complex with a fluorogenic synthetic peptidic substrate with a fluorine atom.

4JQG の概要

• エントリーDOI: 10.2210/pdb4jqg/pdb
• 関連するPDBエントリー: 2OW0 2OW1 4H1Q 4H2E 4H3X 4H82 4HMA 4JIJ 4JXA
• 分子名称: fluorogenic peptidic substrate (8MC)PLG(PFF)(DNW)AR(NH2), SODIUM ION, Matrix metalloproteinase-9, ... (11 entities in total)
• 機能のキーワード: halogen-water-hydrogen bridge, zincin-like, gelatinase, collagenase, catalytic domain, hydrolase-substrate complex, hydrolase/substrate
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted, extracellular space, extracellular matrix : P14780
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 40327.38

構造登録者

Stura, E.A.,Vera, L.,Cassar-Lajeunesse, E.,Tranchant, I.,Amoura, M.,Dive, V. (登録日: 2013-03-20, 公開日: 2014-03-12, 最終更新日: 2023-12-06)

主引用文献

Tranchant, I.,Vera, L.,Czarny, B.,Amoura, M.,Cassar, E.,Beau, F.,Stura, E.A.,Dive, V.
Halogen Bonding Controls Selectivity of FRET Substrate Probes for MMP-9.
Chem.Biol., 21:408-413, 2014

PubMed Abstract: Matrix metalloproteinases (MMPs) are a large family of zinc-dependent endoproteases that catalyze cleavage of extracellular matrix and nonmatrix proteins. MMPs play a role in tissue remodeling, and their uncontrolled activity is associated with number of diseases, including tumor metastasis. Thus, there is a need to develop methods to monitor MMP activity, and number of probes has been previously described. The key problem many probes encounter is the issue of selectivity, since 23 human MMPs, despite playing different physiological roles, have structurally similar active sites. Here, we introduce the halogen bonding concept into the probe design and show that the probe containing iodine exhibits an unprecedented selectivity for MMP-9. We provide structure-based explanation for the selectivity, confirming that it is due to formation of the halogen bond that supports catalysis, and we highlight the value of exploring halogen bonding in the context of selective probe design.

PubMed: 24583051
DOI: 10.1016/j.chembiol.2014.01.008

実験手法

X-RAY DIFFRACTION (1.849 Å)