2AUX

Cathepsin K complexed with a semicarbazone inhibitor

2AUX の概要

• エントリーDOI: 10.2210/pdb2aux/pdb
• 関連するPDBエントリー: 2AUZ
• 分子名称: Cathepsin K, (1R)-2-METHYL-1-(PHENYLMETHYL)PROPYL[(1S)-1-FORMYLPENTYL]CARBAMATE (3 entities in total)
• 機能のキーワード: catk, cysteine protease, 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: 1
• 化学式量合計: 23828.89

構造登録者

Adkison, K.K.,Barrett, D.G.,Deaton, D.N.,Gampe, R.T.,Hassell, A.M.,Long, S.T.,McFadyen, R.B.,Miller, A.B.,Miller, L.R.,Shewchuk, L.M. (登録日: 2005-08-29, 公開日: 2006-08-08, 最終更新日: 2024-10-30)

主引用文献

Adkison, K.K.,Barrett, D.G.,Deaton, D.N.,Gampe, R.T.,Hassell, A.M.,Long, S.T.,McFadyen, R.B.,Miller, A.B.,Miller, L.R.,Payne, J.A.,Shewchuk, L.M.,Wells-Knecht, K.J.,Willard, D.H.,Wright, L.L.
Semicarbazone-based inhibitors of cathepsin K, are they prodrugs for aldehyde inhibitors?
Bioorg.Med.Chem.Lett., 16:978-983, 2006

PubMed Abstract: Starting from potent aldehyde inhibitors with poor drug properties, derivatization to semicarbazones led to the identification of a series of semicarbazone-based cathepsin K inhibitors with greater solubility and better pharmacokinetic profiles than their parent aldehydes. Furthermore, a representative semicarbazone inhibitor attenuated bone resorption in an ex vivo rat calvarial bone resorption model. However, based on enzyme inhibition comparisons at neutral pH, semicarbazone hydrolysis rates, and 13C NMR experiments, these semicarbazones probably function as prodrugs of aldehydes.

PubMed: 16290936
DOI: 10.1016/j.bmcl.2005.10.108

実験手法

X-RAY DIFFRACTION (2.4 Å)