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PDBsum entry 1ptw
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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The crystal structure of AMP-Bound pde4 suggests a mechanism for phosphodiesterase catalysis.
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Authors
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Q.Huai,
J.Colicelli,
H.Ke.
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Ref.
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Biochemistry, 2003,
42,
13220-13226.
[DOI no: ]
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PubMed id
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Abstract
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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.
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