Kinetic and Structural Studies of Phosphodiesterase-8A and Implication on the Inhibitor Selectivity

• Published in: Biochemistry (Easton) Vol. 47; no. 48; pp. 12760 - 12768
• Main Authors: Wang, Huanchen, Yan, Zier, Yang, Serena, Cai, Jiwen, Robinson, Howard, Ke, Hengming
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 02.12.2008
• Subjects: 1-Methyl-3-isobutylxanthine - metabolism; 1-Methyl-3-isobutylxanthine - pharmacology; 3',5'-Cyclic-AMP Phosphodiesterases - antagonists & inhibitors; 3',5'-Cyclic-AMP Phosphodiesterases - chemistry; 3',5'-Cyclic-AMP Phosphodiesterases - genetics; 3',5'-Cyclic-AMP Phosphodiesterases - metabolism; Amino Acid Sequence; Catalytic Domain; Crystallography, X-Ray; Enzyme Inhibitors - metabolism; Enzyme Inhibitors - pharmacology; Escherichia coli - genetics; Humans; Kinetics; Models, Molecular; Molecular Sequence Data; Mutation; Protein Renaturation; Substrate Specificity; Tyrosine

Cyclic nucleotide phosphodiesterase-8 (PDE8) is a family of cAMP-specific enzymes and plays important roles in many biological processes, including T-cell activation, testosterone production, adrenocortical hyperplasia, and thyroid function. However, no PDE8 selective inhibitors are available for tr...