PT  - JOURNAL ARTICLE
AU  - Xu, Robert X.
AU  - Hassell, Anne M.
AU  - Vanderwall, Dana
AU  - Lambert, Millard H.
AU  - Holmes, William D.
AU  - Luther, Michael A.
AU  - Rocque, Warren J.
AU  - Milburn, Michael V.
AU  - Zhao, Yingdong
AU  - Ke, Hengming
AU  - Nolte, Robert T.
TI  - Atomic Structure of PDE4: Insights into Phosphodiesterase Mechanism and Specificity
AID  - 10.1126/science.288.5472.1822
DP  - 2000 Jun 09
TA  - Science
PG  - 1822--1825
VI  - 288
IP  - 5472
4099  - http://science.sciencemag.org/content/288/5472/1822.short
4100  - http://science.sciencemag.org/content/288/5472/1822.full
SO  - Science2000 Jun 09; 288
AB  - 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.