Amino acid sequence of the cyclic GMP stimulated cyclic nucleotide phosphodiesterase from bovine heart.
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.
Trong
H L
HL
Department of Biochemistry, University of Washington, Seattle 98195.
Beier
N
N
Sonnenburg
W K
WK
Stroop
S D
SD
Walsh
K A
KA
Beavo
J A
JA
Charbonneau
H
H
D000595:Amino Acid Sequence; D000818:Animals; D002147:Calmodulin / Q000235:genetics* / Q000302:isolation & purification; D002417:Cattle; D006152:Cyclic GMP / Q000494:pharmacology*; D004247:DNA / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D009206:Myocardium / Q000201:enzymology; D012689:Sequence Homology, Nucleic Acid
D002147:Calmodulin; D005656:Fungal Proteins; D004247:DNA; D006152:Cyclic GMP