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Potential Protein Phosphatase 2A Agents from Traditional Chinese Medicine against Cancer.

Chen KC, Chen HY, Chen CY - Evid Based Complement Alternat Med (2014)

Bottom Line: As an environmental toxin, okadaic acid, is a tumor promoter and binds to PP2A catalytic C subunit and the cancer-associated mutations in PP2A structural A subunit in human tumor tissue; PP2A may have tumor-suppressing function.The results of docking simulation are optimized under dynamic conditions by MD simulations after virtual screening to validate the stability of H-bonds between PP2A- α protein and each ligand.Hence, we propose the TCM compounds, trichosanatine and squamosamide, as potential candidates as lead compounds for further study in drug development process with the PP2A- α protein.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, China Medical University, Taichung 40402, Taiwan.

ABSTRACT
Protein phosphatase 2A (PP2A) is an important phosphatase which regulates various cellular processes, such as protein synthesis, cell growth, cellular signaling, apoptosis, metabolism, and stress responses. It is a holoenzyme composed of the structural A and catalytic C subunits and a regulatory B subunit. As an environmental toxin, okadaic acid, is a tumor promoter and binds to PP2A catalytic C subunit and the cancer-associated mutations in PP2A structural A subunit in human tumor tissue; PP2A may have tumor-suppressing function. It is a potential drug target in the treatment of cancer. In this study, we screen the TCM compounds in TCM Database@Taiwan to investigate the potent lead compounds as PP2A agent. The results of docking simulation are optimized under dynamic conditions by MD simulations after virtual screening to validate the stability of H-bonds between PP2A- α protein and each ligand. The top TCM candidates, trichosanatine and squamosamide, have potential binding affinities and interactions with key residues Arg89 and Arg214 in the docking simulation. In addition, these interactions were stable under dynamic conditions. Hence, we propose the TCM compounds, trichosanatine and squamosamide, as potential candidates as lead compounds for further study in drug development process with the PP2A- α protein.

No MeSH data available.


Related in: MedlinePlus

Disordered disposition predicted by PONDR-Fit.
© Copyright Policy - open-access
Related In: Results  -  Collection


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fig1: Disordered disposition predicted by PONDR-Fit.

Mentions: The result of the disordered residues predicted by PONDR-Fit with the sequence of PP2A-α protein from Swiss-Prot (UniProtKB: P67775) is illustrated in Figure 1. For PP2A-α protein, Figure 1 indicates that the structure of binding domain is stable as the major residues of binding domain do not lie in the disordered region.


Potential Protein Phosphatase 2A Agents from Traditional Chinese Medicine against Cancer.

Chen KC, Chen HY, Chen CY - Evid Based Complement Alternat Med (2014)

Disordered disposition predicted by PONDR-Fit.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4020536&req=5

fig1: Disordered disposition predicted by PONDR-Fit.
Mentions: The result of the disordered residues predicted by PONDR-Fit with the sequence of PP2A-α protein from Swiss-Prot (UniProtKB: P67775) is illustrated in Figure 1. For PP2A-α protein, Figure 1 indicates that the structure of binding domain is stable as the major residues of binding domain do not lie in the disordered region.

Bottom Line: As an environmental toxin, okadaic acid, is a tumor promoter and binds to PP2A catalytic C subunit and the cancer-associated mutations in PP2A structural A subunit in human tumor tissue; PP2A may have tumor-suppressing function.The results of docking simulation are optimized under dynamic conditions by MD simulations after virtual screening to validate the stability of H-bonds between PP2A- α protein and each ligand.Hence, we propose the TCM compounds, trichosanatine and squamosamide, as potential candidates as lead compounds for further study in drug development process with the PP2A- α protein.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, China Medical University, Taichung 40402, Taiwan.

ABSTRACT
Protein phosphatase 2A (PP2A) is an important phosphatase which regulates various cellular processes, such as protein synthesis, cell growth, cellular signaling, apoptosis, metabolism, and stress responses. It is a holoenzyme composed of the structural A and catalytic C subunits and a regulatory B subunit. As an environmental toxin, okadaic acid, is a tumor promoter and binds to PP2A catalytic C subunit and the cancer-associated mutations in PP2A structural A subunit in human tumor tissue; PP2A may have tumor-suppressing function. It is a potential drug target in the treatment of cancer. In this study, we screen the TCM compounds in TCM Database@Taiwan to investigate the potent lead compounds as PP2A agent. The results of docking simulation are optimized under dynamic conditions by MD simulations after virtual screening to validate the stability of H-bonds between PP2A- α protein and each ligand. The top TCM candidates, trichosanatine and squamosamide, have potential binding affinities and interactions with key residues Arg89 and Arg214 in the docking simulation. In addition, these interactions were stable under dynamic conditions. Hence, we propose the TCM compounds, trichosanatine and squamosamide, as potential candidates as lead compounds for further study in drug development process with the PP2A- α protein.

No MeSH data available.


Related in: MedlinePlus