1ptw

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[[Image:1ptw.jpg|left|200px]]<br /><applet load="1ptw" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1ptw.jpg|left|200px]]
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caption="1ptw, resolution 2.3&Aring;" />
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'''The Crystal Structure of AMP-Bound PDE4 Suggests a Mechanism for Phosphodiesterase Catalysis'''<br />
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{{Structure
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|PDB= 1ptw |SIZE=350|CAPTION= <scene name='initialview01'>1ptw</scene>, resolution 2.3&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> and <scene name='pdbligand=AMP:ADENOSINE MONOPHOSPHATE'>AMP</scene>
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|ACTIVITY= [http://en.wikipedia.org/wiki/3',5'-cyclic-nucleotide_phosphodiesterase 3',5'-cyclic-nucleotide phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.17 3.1.4.17]
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|GENE= PDE4D2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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}}
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'''The Crystal Structure of AMP-Bound PDE4 Suggests a Mechanism for Phosphodiesterase Catalysis'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1PTW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=AMP:'>AMP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/3',5'-cyclic-nucleotide_phosphodiesterase 3',5'-cyclic-nucleotide phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.17 3.1.4.17] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PTW OCA].
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1PTW is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PTW OCA].
==Reference==
==Reference==
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The crystal structure of AMP-bound PDE4 suggests a mechanism for phosphodiesterase catalysis., Huai Q, Colicelli J, Ke H, Biochemistry. 2003 Nov 18;42(45):13220-6. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=14609333 14609333]
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The crystal structure of AMP-bound PDE4 suggests a mechanism for phosphodiesterase catalysis., Huai Q, Colicelli J, Ke H, Biochemistry. 2003 Nov 18;42(45):13220-6. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14609333 14609333]
[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: catalytic mechanism]]
[[Category: catalytic mechanism]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:32:30 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:28:53 2008''

Revision as of 11:28, 20 March 2008


PDB ID 1ptw

Drag the structure with the mouse to rotate
, resolution 2.3Å
Ligands: and
Gene: PDE4D2 (Homo sapiens)
Activity: 3',5'-cyclic-nucleotide phosphodiesterase, with EC number 3.1.4.17
Coordinates: save as pdb, mmCIF, xml



The Crystal Structure of AMP-Bound PDE4 Suggests a Mechanism for Phosphodiesterase Catalysis


Contents

Overview

Cyclic nucleotide phosphodiesterases (PDEs) regulate the intracellular concentrations of cyclic 3',5'-adenosine and guanosine monophosphates (cAMP and cGMP, respectively) by hydrolyzing them to AMP and GMP, respectively. Family-selective inhibitors of PDEs have been studied for treatment of various human diseases. However, the catalytic mechanism of cyclic nucleotide hydrolysis by PDEs has remained unclear. We determined the crystal structure of the human PDE4D2 catalytic domain in complex with AMP at 2.4 A resolution. In this structure, two divalent metal ions simultaneously interact with the phosphate group of AMP, implying a binuclear catalysis. In addition, the structure suggested that a hydroxide ion or a water bridging two metal ions may serve as the nucleophile for the hydrolysis of the cAMP phosphodiester bond.

Disease

Known disease associated with this structure: Stroke, susceptibility to, 1 OMIM:[600129]

About this Structure

1PTW is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

The crystal structure of AMP-bound PDE4 suggests a mechanism for phosphodiesterase catalysis., Huai Q, Colicelli J, Ke H, Biochemistry. 2003 Nov 18;42(45):13220-6. PMID:14609333

Page seeded by OCA on Thu Mar 20 13:28:53 2008

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