4IE1

Crystal structure of human Arginase-1 complexed with inhibitor 1h

4IE1 の概要

• エントリーDOI: 10.2210/pdb4ie1/pdb
• 関連するPDBエントリー: 1D3V 2AEB
• 分子名称: Arginase-1, [(5R)-5-amino-5-carboxy-8-hydroxyoctyl](trihydroxy)borate(1-), MANGANESE (II) ION, ... (4 entities in total)
• 機能のキーワード: boron compounds, metalloenzyme, alpha/beta fold, hydrolase, arginine metabolism, manganese, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm : P05089
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 68567.59

構造登録者

Cousido-Siah, A.,Mitschler, A.,Ruiz, F.X.,Beckett, P.,Van Zandt, M.C.,Ji, M.K.,Whitehouse, D.,Ryder, T.,Jagdmann, E.,Andreoli, M.,Mazur, A.,Padmanilayam, M.,Schroeter, H.,Golebiowski, A.,Podjarny, A. (登録日: 2012-12-13, 公開日: 2013-03-20, 最終更新日: 2023-09-20)

主引用文献

Golebiowski, A.,Paul Beckett, R.,Van Zandt, M.,Ji, M.K.,Whitehouse, D.,Ryder, T.R.,Jagdmann, E.,Andreoli, M.,Mazur, A.,Padmanilayam, M.,Cousido-Siah, A.,Mitschler, A.,Ruiz, F.X.,Podjarny, A.,Schroeter, H.
2-Substituted-2-amino-6-boronohexanoic acids as arginase inhibitors.
Bioorg.Med.Chem.Lett., 23:2027-2030, 2013

PubMed Abstract: Substitution at the alpha center of the known human arginase inhibitor 2-amino-6-boronohexanoic acid (ABH) is acceptable in the active site pockets of both human arginase I and arginase II. In particular, substituents with a tertiary amine linked via a two carbon chain show improved inhibitory potency for both enzyme isoforms. This potency improvement can be rationalized by X-ray crystallography, which shows a water-mediated contact between the basic nitrogen and the carboxylic acid side chain of Asp200, which is situated at the mouth of the active site pocket of arginase II (Asp181 in arginase I). We believe that this is the first literature report of compounds with improved arginase inhibitory activity, relative to ABH, and represents a promising starting point for further optimization of in vitro potency and the identification of better tool molecules for in vivo investigations of the potential pathophysiological roles of arginases.

PubMed: 23453840
DOI: 10.1016/j.bmcl.2013.02.024

実験手法

X-RAY DIFFRACTION (2.0006 Å)