Atomic Structure of PDE4: Insights into Phosphodiesterase Mechanism and Specificity

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Science  09 Jun 2000:
Vol. 288, Issue 5472, pp. 1822-1825
DOI: 10.1126/science.288.5472.1822

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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.

  • * Present address: Molecular Statistics and Bioinformatics Section, National Cancer Institute, Bethesda, MD 20892, USA.

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