Structural highlights
Function
[PPP5_HUMAN] May play a role in the regulation of RNA biogenesis and/or mitosis. In vitro, dephosphorylates serine residues of skeletal muscle phosphorylase and histone H1.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Structural basis of serine/threonine phosphatase inhibition by the archetypal small molecules cantharidin and norcantharidin.,Bertini I, Calderone V, Fragai M, Luchinat C, Talluri E J Med Chem. 2009 Aug 13;52(15):4838-43. PMID:19601647[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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. 2009 Aug 13;52(15):4838-43. PMID:19601647 doi:10.1021/jm900610k
