1ptw
The Crystal Structure of AMP-Bound PDE4 Suggests a Mechanism for Phosphodiesterase Catalysis
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OverviewOverview
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.
DiseaseDisease
Known disease associated with this structure: Stroke, susceptibility to, 1 OMIM:[600129]
About this StructureAbout this Structure
1PTW is a Single protein structure of sequence from Homo sapiens with ZN and AMP as ligands. Active as 3',5'-cyclic-nucleotide phosphodiesterase, with EC number 3.1.4.17 Full crystallographic information is available from OCA.
ReferenceReference
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
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