4BX2

Crystal Structure of murine Chronophin (Pyridoxal Phosphate Phosphatase) in complex with Beryllium trifluoride

4BX2 の概要

• エントリーDOI: 10.2210/pdb4bx2/pdb
• 関連するPDBエントリー: 4BX0 4BX3
• 分子名称: PYRIDOXAL PHOSPHATE PHOSPHATASE, MAGNESIUM ION, BERYLLIUM TRIFLUORIDE ION, ... (5 entities in total)
• 機能のキーワード: hydrolase, pdxp, had phosphatase, had-like hydrolase
• 由来する生物種: MUS MUSCULUS (HOUSE MOUSE)
• 細胞内の位置: Cytoplasm, cytosol (By similarity): P60487
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 63686.77

構造登録者

Knobloch, G.,Gohla, A.,Schindelin, H. (登録日: 2013-07-08, 公開日: 2013-12-25, 最終更新日: 2024-10-23)

主引用文献

Kestler, C.,Knobloch, G.,Tessmer, I.,Jeanclos, E.,Schindelin, H.,Gohla, A.
Chronophin Dimerization is Required for Proper Positioning of its Substrate Specificity Loop.
J.Biol.Chem., 289:3094-, 2014

PubMed Abstract: Mammalian phosphatases of the haloacid dehalogenase (HAD) superfamily have emerged as important regulators of physiology and disease. Many of these enzymes are stable homodimers; however, the role of their dimerization is largely unknown. Here, we explore the function of the obligatory homodimerization of chronophin, a mammalian HAD phosphatase known to dephosphorylate pyridoxal 5'-phosphate (PLP) and serine/threonine-phosphorylated proteins. The exchange of two residues in the murine chronophin homodimerization interface (chronophin(A194K,A195K)) yields a constitutive monomer both in vitro and in cells. The catalytic activity of monomeric chronophin toward PLP is strongly impaired. X-ray crystallographic studies of chronophin(A194K,A195K) revealed that dimer formation is essential for an intermolecular arginine-arginine-tryptophan stacking interaction that positions a critical histidine residue in the substrate specificity loop of chronophin for PLP coordination. Analysis of all available crystal structures of HAD hydrolases that are grouped together with chronophin in the C2a-type structural subfamily uncovered a highly conserved mode of dimerization that results in intermolecular contacts involving the substrate specificity loop. Our results explain how the dimerization of HAD hydrolases contributes to their catalytic efficiency and substrate specificity.

PubMed: 24338687
DOI: 10.1074/JBC.M113.536482

実験手法

X-RAY DIFFRACTION (2.193 Å)