3LGG

Crystal structure of human adenosine deaminase growth factor, adenosine deaminase type 2 (ADA2) complexed with transition state analogue, coformycin

3LGG の概要

• エントリーDOI: 10.2210/pdb3lgg/pdb
• 関連するPDBエントリー: 3LGD
• 分子名称: Adenosine deaminase CECR1, 2-acetamido-2-deoxy-beta-D-glucopyranose, ZINC ION, ... (5 entities in total)
• 機能のキーワード: tim barrel, dimerization and receptor binding domains, glycoprotein, hydrolase, growth factor, secreted
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: Q9NZK5
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 120125.19

構造登録者

Zavialov, A.V. (登録日: 2010-01-20, 公開日: 2010-02-09, 最終更新日: 2024-10-30)

主引用文献

Zavialov, A.V.,Yu, X.,Spillmann, D.,Lauvau, G.,Zavialov, A.V.
Structural basis for the growth factor activity of human adenosine deaminase ADA2.
J.Biol.Chem., 285:12367-12377, 2010

PubMed Abstract: Two distinct adenosine deaminases, ADA1 and ADA2, are found in humans. ADA1 has an important role in lymphocyte function and inherited mutations in ADA1 result in severe combined immunodeficiency. The recently isolated ADA2 belongs to the novel family of adenosine deaminase growth factors (ADGFs), which play an important role in tissue development. The crystal structures of ADA2 and ADA2 bound to a transition state analogue presented here reveal the structural basis of the catalytic/signaling activity of ADGF/ADA2 proteins. In addition to the catalytic domain, the structures discovered two ADGF/ADA2-specific domains of novel folds that mediate the protein dimerization and binding to the cell surface receptors. This complex architecture is in sharp contrast with that of monomeric single domain ADA1. An extensive glycosylation and the presence of a conserved disulfide bond and a signal peptide in ADA2 strongly suggest that ADA2, in contrast to ADA1, is specifically designed to act in the extracellular environment. The comparison of catalytic sites of ADA2 and ADA1 demonstrates large differences in the arrangement of the substrate-binding pockets. These structural differences explain the substrate and inhibitor specificity of adenosine deaminases and provide the basis for a rational design of ADA2-targeting drugs to modulate the immune system responses in pathophysiological conditions.

PubMed: 20147294
DOI: 10.1074/jbc.M109.083527

実験手法

X-RAY DIFFRACTION (2.5 Å)