1ptw: Difference between revisions

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==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.

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==

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[[Category: catalytic mechanism]]

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@@ Line 4: / Line 4: @@
 ==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.
+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==
@@ Line 26: / Line 26: @@
 [[Category: catalytic mechanism]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:41:36 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:32:30 2008''