Amino acid sequence of the cyclic GMP stimulated cyclic nucleotide phosphodiesterase from bovine heart

• Published in: Biochemistry (Easton) Vol. 29; no. 44; pp. 10280 - 10288
• Main Authors: Trong, Hai Le, Beier, Norbert, Sonnenburg, William K, Stroop, Steven D, Walsh, Kenneth A, Beavo, Joseph A, Charbonneau, Harry
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01.11.1990
• Subjects: Amino Acid Sequence; Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; Calmodulin - genetics; Calmodulin - isolation & purification; Cattle; Cyclic GMP - pharmacology; DNA - genetics; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Fungal Proteins - genetics; Hydrolases; Molecular Sequence Data; Myocardium - enzymology; Sequence Homology, Nucleic Acid; Heart; Bovine; Gel electrophoresis; Enzyme; Isozyme; HPLC chromatography; 3',5'-GMP; Molecular interaction; Vertebrata; Conserved sequence; Mammalia; Cyclic-nucleotide phosphodiesterase; Regulatory sequence; Dimer; Artiodactyla; Molecular cloning; Mass spectrometry; Ungulata; Aminoacid sequence
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi00496a018

The complete amino acid sequence of the cyclic GMP stimulated cyclic nucleotide phosphodiesterase (cGS-PDE) of bovine heart has been determined by analysis of five digests of the protein; placement of the C-terminal 330 residues has been confirmed by interpretation of the corresponding partial cDNA clone. The holoenzyme is a homodimer of two identical N alpha-acetylated polypeptide chains of 921 residues, each with a calculated molecular weight of 103,244. The C-terminal region, residues 613-871, of the cGS-PDE comprises a catalytic domain that is conserved in all phosphodiesterase sequences except those of PDE 1 from Saccharomyces cerevisiae and a secreted PDE from Dictyostelium. A second conserved region, residues 209-567, is homologous to corresponding regions of the alpha and alpha' subunits of the photoreceptor phosphodiesterases. This conserved domain specifically binds cGMP and is involved in the allosteric regulation of the cGS-PDE. This regulatory domain contains two tandem, internal repeats, suggesting that it evolved from an ancestral gene duplication. Common cyclic nucleotide binding properties and a distant structural relationship provide evidence that the catalytic and regulatory domains within the cGS- and photoreceptor PDEs are also related by an ancient internal gene duplication.