6WZV

Lon protease proteolytic domain

6WZV の概要

• エントリーDOI: 10.2210/pdb6wzv/pdb
• 関連するPDBエントリー: 6WYS
• 分子名称: Lon protease homolog, mitochondrial, N-[(1R)-1-borono-3-methylbutyl]-Nalpha-(pyrazine-2-carbonyl)-D-phenylalaninamide, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: proteolytic domain, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 72517.39

構造登録者

Lee, C.C.,Spraggon, G. (登録日: 2020-05-14, 公開日: 2021-04-14, 最終更新日: 2024-10-23)

主引用文献

Kingsley, L.J.,He, X.,McNeill, M.,Nelson, J.,Nikulin, V.,Ma, Z.,Lu, W.,Zhou, V.W.,Manuia, M.,Kreusch, A.,Gao, M.Y.,Witmer, D.,Vaillancourt, M.T.,Lu, M.,Greenblatt, S.,Lee, C.,Vashisht, A.,Bender, S.,Spraggon, G.,Michellys, P.Y.,Jia, Y.,Haling, J.R.,Lelais, G.
Structure-Based Design of Selective LONP1 Inhibitors for Probing In Vitro Biology.
J.Med.Chem., 64:4857-4869, 2021

PubMed Abstract: LONP1 is an AAA+ protease that maintains mitochondrial homeostasis by removing damaged or misfolded proteins. Elevated activity and expression of LONP1 promotes cancer cell proliferation and resistance to apoptosis-inducing reagents. Despite the importance of LONP1 in human biology and disease, very few LONP1 inhibitors have been described in the literature. Herein, we report the development of selective boronic acid-based LONP1 inhibitors using structure-based drug design as well as the first structures of human LONP1 bound to various inhibitors. Our efforts led to several nanomolar LONP1 inhibitors with little to no activity against the 20S proteasome that serve as tool compounds to investigate LONP1 biology.

PubMed: 33821636
DOI: 10.1021/acs.jmedchem.0c02152

実験手法

X-RAY DIFFRACTION (2.51 Å)