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Updated: Jul 9, 2026

Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog
Published on: November 5, 2014
Atomic structure of PDE4: insights into phosphodiesterase mechanism and specificity
R X Xu1, A M Hassell, D Vanderwall
1Department of Structural Chemistry, Department of Molecular Sciences, Glaxo Wellcome Research and Development, Research Triangle Park, NC 27709, USA.
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.
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