7NXM

Structure of human cathepsin K in complex with the selective activity-based probe Gu3416

7NXM の概要

• エントリーDOI: 10.2210/pdb7nxm/pdb
• 分子名称: Cathepsin K, SULFATE ION, N-(4-(dibenzylamino)-4-oxobutyl)-2-(5-(dimethylamino)pentanamido)-4-methylpentanamide, ... (4 entities in total)
• 機能のキーワード: hydrolase, inhibitor, complex, activity-based probe, acrylamide inhibitor
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 24299.46

構造登録者

Busa, M.,Benysek, J.,Lemke, C.,Gutschow, M.,Mares, M. (登録日: 2021-03-18, 公開日: 2021-09-08, 最終更新日: 2024-11-20)

主引用文献

Lemke, C.,Benysek, J.,Brajtenbach, D.,Breuer, C.,Jilkova, A.,Horn, M.,Busa, M.,Ulrychova, L.,Illies, A.,Kubatzky, K.F.,Bartz, U.,Mares, M.,Gutschow, M.
An Activity-Based Probe for Cathepsin K Imaging with Excellent Potency and Selectivity.
J.Med.Chem., 64:13793-13806, 2021

PubMed Abstract: The cysteine protease cathepsin K is a target for the treatment of diseases associated with high bone turnover. Cathepsin K is mainly expressed in osteoclasts and responsible for the destruction of the proteinaceous components of the bone matrix. We designed various fluorescent activity-based probes (ABPs) and their precursors that bind to and inactivate cathepsin K. ABP exhibited extraordinary potency (/ = 35,300 Ms) and selectivity for human cathepsin K. Crystal structures of cathepsin K in complex with ABP and its nonfluorescent precursor were determined to characterize the binding mode of this new type of acrylamide-based Michael acceptor with the particular orientation of the dibenzylamine moiety to the primed subsite region. The cyanine-5 containing probe allowed for sensitive detection of cathepsin K, selective visualization in complex proteomes, and live cell imaging of a human osteosarcoma cell line, underlining its applicability in a pathophysiological environment.

PubMed: 34473502
DOI: 10.1021/acs.jmedchem.1c01178

実験手法

X-RAY DIFFRACTION (1.72 Å)