2QLL

Human liver glycogen phosphorylase- GL complex

2QLL の概要

• エントリーDOI: 10.2210/pdb2qll/pdb
• 関連するPDBエントリー: 1FA9 1FC0
• 分子名称: Glycogen phosphorylase, liver form, protein targeting to glycogen - GL, PYRIDOXAL-5'-PHOSPHATE, ... (4 entities in total)
• 機能のキーワード: drug discovery, glycogen metabolism, protein-protein interaction, allosteric enzyme, carbohydrate metabolism, disease mutation, glycogen storage disease, glycosyltransferase, nucleotide-binding, phosphorylation, pyridoxal phosphate, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 98102.12

構造登録者

Pautsch, A.,Streicher, R.,Wissdorf, O.,Stadler, N. (登録日: 2007-07-13, 公開日: 2008-02-19, 最終更新日: 2013-03-13)

主引用文献

Pautsch, A.,Stadler, N.,Wissdorf, O.,Langkopf, E.,Moreth, W.,Streicher, R.
Molecular recognition of the protein phosphatase 1 glycogen targeting subunit by glycogen phosphorylase.
J.Biol.Chem., 283:8913-8918, 2008

PubMed Abstract: Disrupting the interaction between glycogen phosphorylase and the glycogen targeting subunit (G(L)) of protein phosphatase 1 is emerging as a novel target for the treatment of type 2 diabetes. To elucidate the molecular basis of binding, we have determined the crystal structure of liver phosphorylase bound to a G(L)-derived peptide. The structure reveals the C terminus of G(L) binding in a hydrophobically collapsed conformation to the allosteric regulator-binding site at the phosphorylase dimer interface. G(L) mimics interactions that are otherwise employed by the activator AMP. Functional studies show that G(L) binds tighter than AMP and confirm that the C-terminal Tyr-Tyr motif is the major determinant for G(L) binding potency. Our study validates the G(L)-phosphorylase interface as a novel target for small molecule interaction.

PubMed: 18198182
DOI: 10.1074/jbc.M706612200

実験手法

X-RAY DIFFRACTION (2.56 Å)