5CUH

Crystal structure MMP-9 complexes with a constrained hydroxamate based inhibitor LT4

5CUH の概要

• エントリーDOI: 10.2210/pdb5cuh/pdb
• 分子名称: Matrix metalloproteinase-9,Matrix metalloproteinase-9, ZINC ION, CALCIUM ION, ... (8 entities in total)
• 機能のキーワード: mmp-9 hydroxamate-based inhibitor gelatinase, hydrolase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Secreted, extracellular space, extracellular matrix : P14780
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 38480.33

構造登録者

Tepshi, L.,Vera, L.,Nuti, E.,Rosalia, L.,Rossello, A.,Stura, E.A. (登録日: 2015-07-24, 公開日: 2016-02-10, 最終更新日: 2023-11-08)

主引用文献

Camodeca, C.,Nuti, E.,Tepshi, L.,Boero, S.,Tuccinardi, T.,Stura, E.A.,Poggi, A.,Zocchi, M.R.,Rossello, A.
Discovery of a new selective inhibitor of A Disintegrin And Metalloprotease 10 (ADAM-10) able to reduce the shedding of NKG2D ligands in Hodgkin's lymphoma cell models.
Eur.J.Med.Chem., 111:193-201, 2016

PubMed Abstract: Hodgkin's lymphoma (HL) is the most common malignant lymphoma in young adults in the western world. This disease is characterized by an overexpression of ADAM-10 with increased release of NKG2D ligands, involved in an impaired immune response against tumor cells. We designed and synthesized two new ADAM-10 selective inhibitors, 2 and 3 based on previously published ADAM-17 selective inhibitor 1. The most promising compound was the thiazolidine derivative 3, with nanomolar activity for ADAM-10, high selectivity over ADAM-17 and MMPs and good efficacy in reducing the shedding of NKG2D ligands (MIC-B and ULBP3) in three different HL cell lines at non-toxic doses. Molecular modeling studies were used to drive the design and X-ray crystallography studies were carried out to explain the selectivity of 3 for ADAM-10 over MMPs.

PubMed: 26871660
DOI: 10.1016/j.ejmech.2016.01.053

実験手法

X-RAY DIFFRACTION (1.83 Å)