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Epigallocatechin gallate (EGCG) inhibits type II phosphatidylinositol 4-kinases: A key component in pathways of phosphoinositide turnover

► EGCG inhibits type II Phosphatidylinositol (PtdIns) 4-kinase α and β isoforms. ► EGCG has differential interaction with both the isoforms revealed by spectroscopy. ► Autodock mapped the binding residues at ATP binding domain of PtdIns 4-kinase. Type II phosphatidylinositol (PtdIns) 4-kinases produ...

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Published in:Archives of biochemistry and biophysics 2011-12, Vol.516 (1), p.45-51
Main Authors: Sinha, Ranjeet K., Patel, Ronak Y., Bojjireddy, Naveen, Datta, Anindya, Subrahmanyam, Gosukonda
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container_title Archives of biochemistry and biophysics
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creator Sinha, Ranjeet K.
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description ► EGCG inhibits type II Phosphatidylinositol (PtdIns) 4-kinase α and β isoforms. ► EGCG has differential interaction with both the isoforms revealed by spectroscopy. ► Autodock mapped the binding residues at ATP binding domain of PtdIns 4-kinase. Type II phosphatidylinositol (PtdIns) 4-kinases produce PtdIns 4-phosphate, an early key signaling molecule in phosphatidylinositol cycle, which is indispensable for T cell activation. Type II PtdIns 4-kinase alpha and beta have similar biochemical properties. To distinguish these isoforms Epigallocatechin gallate (EGCG) has been evaluated as a specific inhibitor. EGCG is the major active catechin in green tea having anti-inflammatory, antiatherogenic and cancer chemopreventive properties. The precise mechanism of actions and molecular targets of EGCG in early signaling cascades are not well understood. In the present study, we have shown that EGCG inhibits type II PtdIns 4-kinases (α and β isoforms) and PtdIns 3-kinase activity in vitro. EGCG directly bind to both alpha and beta isoforms of type II PtdIns 4-kinases with a Kd of 2.62 μM and 1.02 μM, respectively. Type II PtdIns 4-kinase-EGCG complex have different binding pattern at its excited state. Both isoforms showed significant change in helicity upon binding with EGCG. EGCG modulates its effect by interacting with ATP binding pocket; the residues likely to be involved in EGCG binding were predicted by Autodock. Our findings suggest that EGCG inhibits two isoforms and could be a key to regulate T cell activation.
doi_str_mv 10.1016/j.abb.2011.09.005
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Type II phosphatidylinositol (PtdIns) 4-kinases produce PtdIns 4-phosphate, an early key signaling molecule in phosphatidylinositol cycle, which is indispensable for T cell activation. Type II PtdIns 4-kinase alpha and beta have similar biochemical properties. To distinguish these isoforms Epigallocatechin gallate (EGCG) has been evaluated as a specific inhibitor. EGCG is the major active catechin in green tea having anti-inflammatory, antiatherogenic and cancer chemopreventive properties. The precise mechanism of actions and molecular targets of EGCG in early signaling cascades are not well understood. In the present study, we have shown that EGCG inhibits type II PtdIns 4-kinases (α and β isoforms) and PtdIns 3-kinase activity in vitro. EGCG directly bind to both alpha and beta isoforms of type II PtdIns 4-kinases with a Kd of 2.62 μM and 1.02 μM, respectively. Type II PtdIns 4-kinase-EGCG complex have different binding pattern at its excited state. 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Both isoforms showed significant change in helicity upon binding with EGCG. EGCG modulates its effect by interacting with ATP binding pocket; the residues likely to be involved in EGCG binding were predicted by Autodock. 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Type II phosphatidylinositol (PtdIns) 4-kinases produce PtdIns 4-phosphate, an early key signaling molecule in phosphatidylinositol cycle, which is indispensable for T cell activation. Type II PtdIns 4-kinase alpha and beta have similar biochemical properties. To distinguish these isoforms Epigallocatechin gallate (EGCG) has been evaluated as a specific inhibitor. EGCG is the major active catechin in green tea having anti-inflammatory, antiatherogenic and cancer chemopreventive properties. The precise mechanism of actions and molecular targets of EGCG in early signaling cascades are not well understood. In the present study, we have shown that EGCG inhibits type II PtdIns 4-kinases (α and β isoforms) and PtdIns 3-kinase activity in vitro. EGCG directly bind to both alpha and beta isoforms of type II PtdIns 4-kinases with a Kd of 2.62 μM and 1.02 μM, respectively. Type II PtdIns 4-kinase-EGCG complex have different binding pattern at its excited state. Both isoforms showed significant change in helicity upon binding with EGCG. EGCG modulates its effect by interacting with ATP binding pocket; the residues likely to be involved in EGCG binding were predicted by Autodock. Our findings suggest that EGCG inhibits two isoforms and could be a key to regulate T cell activation.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>21964243</pmid><doi>10.1016/j.abb.2011.09.005</doi><tpages>7</tpages></addata></record>
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ispartof Archives of biochemistry and biophysics, 2011-12, Vol.516 (1), p.45-51
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subjects 1-Phosphatidylinositol 4-Kinase - antagonists & inhibitors
1-Phosphatidylinositol 4-Kinase - chemistry
1-Phosphatidylinositol 4-Kinase - metabolism
adenosine triphosphate
Amino Acid Sequence
Anticarcinogenic Agents - pharmacology
Binding Sites
Camellia sinensis - chemistry
catechin
Catechin - analogs & derivatives
Catechin - pharmacology
chemoprevention
Enzyme Inhibitors - pharmacology
epigallocatechin
Epigallocatechin gallate
green tea
Humans
Jurkat Cells
mechanism of action
Models, Molecular
Molecular Sequence Data
Neoplasms - prevention & control
Phosphatidylinositol 4-kinase
Phosphatidylinositols - metabolism
Protein Binding
Protein Isoforms - antagonists & inhibitors
Protein Isoforms - chemistry
Protein Isoforms - metabolism
Sequence Alignment
T cell activation
T-lymphocytes
title Epigallocatechin gallate (EGCG) inhibits type II phosphatidylinositol 4-kinases: A key component in pathways of phosphoinositide turnover
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