3NH4

Crystal structure of murine aminoacylase 3

3NH4 の概要

• エントリーDOI: 10.2210/pdb3nh4/pdb
• 関連するPDBエントリー: 3NFZ 3NH5 3NH8
• 分子名称: Aspartoacylase-2, ZINC ION, CESIUM ION, ... (7 entities in total)
• 機能のキーワード: mercapturates, hydrolase
• 由来する生物種: Mus musculus (mouse)
• 細胞内の位置: Apical cell membrane; Peripheral membrane protein: Q91XE4
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 37000.61

構造登録者

Hsieh, J.M.,Tsirulnikov, K.,Sawaya, M.R.,Magilnick, N.,Abuladze, N.,Kurtz, I.,Abramson, J.,Pushkin, A. (登録日: 2010-06-14, 公開日: 2010-10-20, 最終更新日: 2023-09-06)

主引用文献

Hsieh, J.M.,Tsirulnikov, K.,Sawaya, M.R.,Magilnick, N.,Abuladze, N.,Kurtz, I.,Abramson, J.,Pushkin, A.
Structures of aminoacylase 3 in complex with acetylated substrates.
Proc.Natl.Acad.Sci.USA, 107:17962-17967, 2010

PubMed Abstract: Trichloroethylene (TCE) is one of the most widespread environmental contaminants, which is metabolized to N-acetyl-S-1,2-dichlorovinyl-L-cysteine (NA-DCVC) before being excreted in the urine. Alternatively, NA-DCVC can be deacetylated by aminoacylase 3 (AA3), an enzyme that is highly expressed in the kidney, liver, and brain. NA-DCVC deacetylation initiates the transformation into toxic products that ultimately causes acute renal failure. AA3 inhibition is therefore a target of interest to prevent TCE induced nephrotoxicity. Here we report the crystal structure of recombinant mouse AA3 (mAA3) in the presence of its acetate byproduct and two substrates: N(α)-acetyl-L-tyrosine and NA-DCVC. These structures, in conjunction with biochemical data, indicated that AA3 mediates substrate specificity through van der Waals interactions providing a dynamic interaction interface, which facilitates a diverse range of substrates.

PubMed: 20921362
DOI: 10.1073/pnas.1006687107

実験手法

X-RAY DIFFRACTION (2 Å)