3HB1

Crystal structure of ed-eya2 complexed with Alf3

3HB1 の概要

• エントリーDOI: 10.2210/pdb3hb1/pdb
• 関連するPDBエントリー: 3HB0
• 分子名称: Eyes absent homolog 2 (Drosophila), ALUMINUM FLUORIDE, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: alpha/beta hydrolase, hydrolase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 124706.54

構造登録者

Jung, S.K.,Jeong, D.G.,Ryu, S.E.,Kim, S.J. (登録日: 2009-05-03, 公開日: 2009-12-01, 最終更新日: 2023-11-01)

主引用文献

Jung, S.K.,Jeong, D.G.,Chung, S.J.,Kim, J.H.,Park, B.C.,Tonks, N.K.,Ryu, S.E.,Kim, S.J.
Crystal structure of ED-Eya2: insight into dual roles as a protein tyrosine phosphatase and a transcription factor
Faseb J., 24:560-569, 2010

PubMed Abstract: Eya proteins are transcription factors that play pivotal roles in organ formation during development by mediating interactions between Sine Oculis (SO) and Dachshund (DAC). Remarkably, the transcriptional activity of Eya proteins is regulated by a dephosphorylating activity within its Eya domain (ED). However, the molecular basis for the link between catalytic and transcriptional activities remains unclear. Here we report the first description of the crystal structure of the ED of human Eya2 (ED-Eya2), determined at 2.4-A resolution. In stark contrast to other members of the haloacid dehalogenase (HAD) family to which ED-Eya2 belongs, the helix-bundle motif (HBM) is elongated along the back of the catalytic site. This not only results in a structure that accommodates large protein substrates but also positions the catalytic and the SO-interacting sites on opposite faces, which suggests that SO binding is not directly affected by catalytic function. Based on the observation that the DAC-binding site is located between the catalytic core and SO binding sites within ED-Eya2, we propose that catalytic activity can be translated to SO binding through DAC, which acts as a transcriptional switch. We also captured at two stages of reaction cycles-acyl-phosphate intermediate and transition state of hydrolysis step, which provided a detailed view of reaction mechanism. The ED-Eya2 structure defined here serves as a model for other members of the Eya family and provides a framework for understanding the role of Eya phosphatase mutations in disease.

PubMed: 19858093
DOI: 10.1096/fj.09-143891

実験手法

X-RAY DIFFRACTION (2.51 Å)