1PTW
The Crystal Structure of AMP-Bound PDE4 Suggests a Mechanism for Phosphodiesterase Catalysis
Summary for 1PTW
| Entry DOI | 10.2210/pdb1ptw/pdb |
| Descriptor | cAMP-specific phosphodiesterase PDE4D2, ZINC ION, ADENOSINE MONOPHOSPHATE, ... (4 entities in total) |
| Functional Keywords | catalytic mechanism, camp hydrolysis crystal structure, binuclear catalysis, hydrolase |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm (By similarity): Q08499 |
| Total number of polymer chains | 4 |
| Total formula weight | 167491.25 |
| Authors | Huai, Q.,Colicelli, J.,Ke, H. (deposition date: 2003-06-23, release date: 2003-11-11, Last modification date: 2024-02-14) |
| Primary citation | Huai, Q.,Colicelli, J.,Ke, H. The crystal structure of AMP-bound PDE4 suggests a mechanism for phosphodiesterase catalysis Biochemistry, 42:13220-13226, 2003 Cited by PubMed Abstract: 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. PubMed: 14609333DOI: 10.1021/bi034653e PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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