Atomic Structure of PDE4: Insights into Phosphodiesterase Mechanism and Specificity
- 9 June 2000
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 288 (5472) , 1822-1825
- https://doi.org/10.1126/science.288.5472.1822
Abstract
Cyclic nucleotides are second messengers that are essential in vision, muscle contraction, neurotransmission, exocytosis, cell growth, and differentiation. These molecules are degraded by a family of enzymes known as phosphodiesterases, which serve a critical function by regulating the intracellular concentration of cyclic nucleotides. We have determined the three-dimensional structure of the catalytic domain of phosphodiesterase 4B2B to 1.77 angstrom resolution. The active site has been identified and contains a cluster of two metal atoms. The structure suggests the mechanism of action and basis for specificity and will provide a framework for structure-assisted drug design for members of the phosphodiesterase family.Keywords
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