1WOH

Crystal Structure of Agmatinase Reveals Structural Conservation and Inhibition Mechanism of the Ureohydrolase Superfamily

1WOH の概要

• エントリーDOI: 10.2210/pdb1woh/pdb
• 関連するPDBエントリー: 1WOG 1WOI
• 分子名称: agmatinase (2 entities in total)
• 機能のキーワード: alpha/beta fold, hydrolase
• 由来する生物種: Deinococcus radiodurans
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 196020.44

構造登録者

Ahn, H.J.,Kim, K.H.,Lee, J.,Ha, J.-Y.,Lee, H.H.,Kim, D.,Yoon, H.-J.,Kwon, A.-R.,Suh, S.W. (登録日: 2004-08-18, 公開日: 2004-09-07, 最終更新日: 2024-03-13)

主引用文献

Ahn, H.J.,Kim, K.H.,Lee, J.,Ha, J.-Y.,Lee, H.H.,Kim, D.,Yoon, H.-J.,Kwon, A.-R.,Suh, S.W.
Crystal structure of agmatinase reveals structural conservation and inhibition mechanism of the ureohydrolase superfamily
J.Biol.Chem., 279:50505-50513, 2004

PubMed Abstract: Agmatine is the product of arginine decarboxylation and can be hydrolyzed by agmatinase to putrescine, the precursor for biosynthesis of higher polyamines, spermidine, and spermine. Besides being an intermediate in polyamine metabolism, recent findings indicate that agmatine may play important regulatory roles in mammals. Agmatinase is a binuclear manganese metalloenzyme and belongs to the ureohydrolase superfamily that includes arginase, formiminoglutamase, and proclavaminate amidinohydrolase. Compared with a wealth of structural information available for arginases, no three-dimensional structure of agmatinase has been reported. Agmatinase from Deinococcus radiodurans, a 304-residue protein, shows approximately 33% of sequence identity to human mitochondrial agmatinase. Here we report the crystal structure of D. radiodurans agmatinase in Mn(2+)-free, Mn(2+)-bound, and Mn(2+)-inhibitor-bound forms, representing the first structure of agmatinase. It reveals the conservation as well as variation in folding, oligomerization, and the active site of the ureohydrolase superfamily. D. radiodurans agmatinase exists as a compact homohexamer of 32 symmetry. Its binuclear manganese cluster is highly similar but not identical to the clusters of arginase and proclavaminate amidinohydrolase. The structure of the inhibited complex reveals that inhibition by 1,6-diaminohexane arises from the displacement of the metal-bridging water.

PubMed: 15355972
DOI: 10.1074/jbc.M409246200

実験手法

X-RAY DIFFRACTION (1.75 Å)