5JA7

Human cathepsin K mutant C25S in complex with the allosteric effector NSC94914

5JA7 の概要

• エントリーDOI: 10.2210/pdb5ja7/pdb
• 分子名称: Cathepsin K, [([1,1'-biphenyl]-2-yl)methyl]propanedioic acid, SULFATE ION, ... (6 entities in total)
• 機能のキーワード: allostery cysteine peptidase proteolysis enzyme regulation collagenase, hydrolase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Lysosome: P43235
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 49962.92

構造登録者

Novinec, M.,Korenc, M.,Lenarcic, B. (登録日: 2016-04-12, 公開日: 2016-11-30, 最終更新日: 2024-10-16)

主引用文献

Novinec, M.,Rebernik, M.,Lenarcic, B.
An allosteric site enables fine-tuning of cathepsin K by diverse effectors.
FEBS Lett., 590:4507-4518, 2016

PubMed Abstract: The cysteine peptidase cathepsin K is a potent collagenolytic enzyme and a promising target for the treatment of osteoporosis. Here, we characterize its allosteric fine-tuning via a recently identified allosteric site. We show that compound NSC94914 binds this site and acts as a specific partial inhibitor of the collagenolytic activity of cathepsin K. We link the functional differences between NSC94914 and known effectors (compound NSC11345 and glycosaminoglycans) to their different modes of interaction with the site. We characterize the allosteric site by site-directed mutagenesis and show that it is involved in specific regulation of the collagenolytic activity of cathepsin K.

PubMed: 27859061
DOI: 10.1002/1873-3468.12495

実験手法

X-RAY DIFFRACTION (1.61 Å)