3H66

Catalytic domain of human Serine/Threonine Phosphatase 5 (PP5c) with two Zn2+ atoms

Summary for 3H66

• Entry DOI: 10.2210/pdb3h66/pdb
• Related: 3H60 3H61 3H62 3H63 3H64 3H67 3H68 3H69
• Descriptor: Serine/threonine-protein phosphatase 5, ZINC ION (3 entities in total)
• Functional Keywords: metalloenzyme, phosphatase, cytoplasm, hydrolase, iron, manganese, metal-binding, nucleus, protein phosphatase, tpr repeat
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: P53041
• Total number of polymer chains: 2
• Total formula weight: 72163.23

Authors

Bertini, I.,Calderone, V.,Fragai, M.,Luchinat, C.,Talluri, E. (deposition date: 2009-04-23, release date: 2009-09-29, Last modification date: 2023-11-01)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.59 Å)