View source for 1ptw

[[Image:1ptw.jpg|left|200px]]

 {{Structure
|PDB= 1ptw |SIZE=350|CAPTION= <scene name='initialview01'>1ptw</scene>, resolution 2.3&Aring;
|SITE= 
|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> and <scene name='pdbligand=AMP:ADENOSINE MONOPHOSPHATE'>AMP</scene>
|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] 
|GENE= PDE4D2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
}}

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


==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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600129 600129]]

==About this Structure==
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==
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: Homo sapiens]]
[[Category: Single protein]]
[[Category: Colicelli, J.]]
[[Category: Huai, Q.]]
[[Category: Ke, H.]]
[[Category: AMP]]
[[Category: ZN]]
[[Category: binuclear catalysis]]
[[Category: camp hydrolysis crystal structure]]
[[Category: catalytic mechanism]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:28:53 2008''