1T5F

arginase I-AOH complex

1T5F の概要

• エントリーDOI: 10.2210/pdb1t5f/pdb
• 分子名称: Arginase 1, MANGANESE (II) ION, (S)-2-AMINO-7,7-DIHYDROXYHEPTANOIC ACID, ... (4 entities in total)
• 機能のキーワード: arginase, aoh, hydrolase
• 由来する生物種: Rattus norvegicus (Norway rat)
• 細胞内の位置: Cytoplasm: P07824
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 102401.07

構造登録者

Shin, H.,Cama, E.,Christianson, D.W. (登録日: 2004-05-04, 公開日: 2005-05-17, 最終更新日: 2024-02-14)

主引用文献

Shin, H.,Cama, E.,Christianson, D.W.
Design of amino acid aldehydes as transition-state analogue inhibitors of arginase
J.Am.Chem.Soc., 126:10278-10284, 2004

PubMed Abstract: Arginase is a binuclear manganese metalloenzyme that catalyzes the hydrolysis of l-arginine to form l-ornithine and urea. Chiral L-amino acids bearing aldehyde side chains have been synthesized in which the electrophilic aldehyde C=O bond is isosteric with the C=N bond of L-arginine. This substitution is intended to facilitate nucleophilic attack by the metal-bridging hydroxide ion upon binding to the arginase active site. Syntheses of the amino acid aldehydes have been accomplished by reduction, oxidation, and Wittig-type reaction with a commercially available derivative of L-glutamic acid. Amino acid aldehydes exhibit inhibition in the micromolar range, and the X-ray crystal structure of arginase I complexed with one of these inhibitors, (S)-2-amino-7-oxoheptanoic acid, has been determined at 2.2 A resolution. In the enzyme-inhibitor complex, the inhibitor aldehyde moiety is hydrated to form the gem-diol: one hydroxyl group bridges the Mn(2+)(2) cluster and donates a hydrogen bond to D128, and the second hydroxyl group donates a hydrogen bond to E277. The binding mode of the neutral gem-diol may mimic the binding of the neutral tetrahedral intermediate and its flanking transition states in arginase catalysis.

PubMed: 15315440
DOI: 10.1021/ja047788w

実験手法

X-RAY DIFFRACTION (2.2 Å)