| Identification of chaulmoogric acid as a small molecule activator of protein phosphatase 5. | |
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MedLine Citation:
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PMID: 19404779 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Protein phosphatase 5 (PP5) is an important protein phosphatase that is abundantly expressed in the central nervous system. Recent studies showed that PP5 activity in the neocortex from patients with Alzheimer's disease (AD) is decreased significantly, suggesting that small molecule PP5 activator may have therapeutic potential for AD. We performed a biochemical screening for PP5 activators with the microsource compound library. Chaulmoogric acid was identified to be an effective activator with EC(50) value of 134.5 microM. Importantly, results from circular dichroism (CD) and limited proteolysis study showed that chaulmoogric acid binds to a region of tetratricopeptide repeat (TPR) domain of PP5 resulting in complete loss of helical contents. These results demonstrate a different mechanism of action from that of arachidonic acid, a known activator for PP5 dephosphorylation activity. Synergistic activation of PP5 enzymatic activity was also observed with combined application of both compounds at relatively low concentrations. Therefore, further structure activity relationship study of chaulmoogric acid may facilitate the discovery of small molecules that can synergize with endogenous arachidonic acid for PP5 activation. |
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Authors:
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Charmian Cher; Marie-Helene Tremblay; Jack R Barber; Shi Chung Ng; Bin Zhang |
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Publication Detail:
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Type: Journal Article Date: 2009-04-30 |
Journal Detail:
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Title: Applied biochemistry and biotechnology Volume: 160 ISSN: 1559-0291 ISO Abbreviation: Appl. Biochem. Biotechnol. Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-02-10 Completed Date: 2010-05-03 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8208561 Medline TA: Appl Biochem Biotechnol Country: United States |
Other Details:
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Languages: eng Pagination: 1450-9 Citation Subset: IM |
Affiliation:
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Department of Biology, CytRx Corporation, 3030 Bunker Hill Street, Suite 101, San Diego, CA 92109, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Arachidonic Acid
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chemistry,
pharmacology Biological Assay Circular Dichroism Enzyme Activation / drug effects Enzyme Activators / chemistry, pharmacology* Fatty Acids / chemistry, pharmacology* Molecular Weight Nitrophenols / metabolism Nuclear Proteins / chemistry, metabolism* Organophosphorus Compounds / metabolism Phosphoprotein Phosphatases / chemistry, metabolism* Protein Processing, Post-Translational / drug effects Protein Structure, Tertiary Small Molecule Libraries / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Activators; 0/Fatty Acids; 0/Nitrophenols; 0/Nuclear Proteins; 0/Organophosphorus Compounds; 0/Small Molecule Libraries; 29106-32-9/chaulmoogric acid; 330-13-2/nitrophenylphosphate; 506-32-1/Arachidonic Acid; EC 3.1.3.16/Phosphoprotein Phosphatases; EC 3.1.3.16/protein phosphatase 5 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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