3H68

Catalytic domain of human Serine/Threonine Phosphatase 5 (PP5c)with two Zn2+ atoms originally soaked with cantharidin (which is present in the structure in the hydrolyzed form)

3H68 の概要

• エントリーDOI: 10.2210/pdb3h68/pdb
• 関連するPDBエントリー: 3H60 3H61 3H62 3H63 3H64 3H66 3H67 3H69
• 分子名称: Serine/threonine-protein phosphatase 5, ZINC ION, (1R,2S,3R,4S)-2,3-dimethyl-7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic acid, ... (4 entities in total)
• 機能のキーワード: metalloenzyme, phosphatase, inhibitors, drug design, cytoplasm, hydrolase, iron, manganese, metal-binding, nucleus, protein phosphatase, tpr repeat
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: P53041
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 72591.66

構造登録者

Bertini, I.,Calderone, V.,Fragai, M.,Luchinat, C.,Talluri, E. (登録日: 2009-04-23, 公開日: 2009-09-29, 最終更新日: 2023-11-01)

主引用文献

Bertini, I.,Calderone, V.,Fragai, M.,Luchinat, C.,Talluri, E.
Structural basis of serine/threonine phosphatase inhibition by the archetypal small molecules cantharidin and norcantharidin
J.Med.Chem., 52:4838-4843, 2009

PubMed Abstract: The inhibition of a subgroup of human serine/threonine protein phosphatases is responsible for the cytotoxicity of cantharidin and norcantharidin against tumor cells. It is shown that the anhydride rings of cantharidin and norcantharidin are hydrolyzed when bound to the catalytic domain of the human serine/threonine protein phosphatases 5 (PP5c), and the high-resolution crystal structures of PP5c complexed with the corresponding dicarboxylic acid derivatives of the two molecules are reported. Norcantharidin shows a unique binding conformation with the catalytically active Mn2PP5c, while cantharidin is characterized by a double conformation in its binding mode to the protein. Different binding modes of norcantharidin are observed depending of whether the starting ligand is in the anhydride or in the dicarboxylic acid form. All these structures will provide the basis for the rational design of new cantharidin-based drugs.

PubMed: 19601647
DOI: 10.1021/jm900610k

実験手法

X-RAY DIFFRACTION (1.5 Å)