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Identification and characterization of a novel family of cyclic nucleotide phosphodiesterases.

Publication ,  Journal Article
Soderling, SH; Bayuga, SJ; Beavo, JA
Published in: J Biol Chem
June 19, 1998

We report the cloning, expression, and characterization of a new family of cyclic nucleotide phosphodiesterase (PDE) that has unique kinetic and inhibitor specificities. A clone corresponding to the C terminus of this PDE was initially identified by a bioinformatic approach and used to isolate a cDNA that is likely full-length. This novel PDE, designated as MMPDE9A1, shows highest mRNA expression in kidney with lower levels in liver, lung, and brain. The mRNA size by Northern blot analysis is approximately 2.0 kilobases, and the cDNA encoding PDE9A1 is 1929 base pairs in length. The largest open reading frame predicts a protein of 534 amino acids with a molecular mass of 62,000 Da. When expressed in COS-7 cells, PDE9A1 activity was not inhibited well by either the nonselective inhibitor 3-isobutyl-1-methyl-xanthine or the new selective PDE5 inhibitor, sildenafil, but it is inhibited by the PDE1/5 inhibitor (+)-cis-5,6a, 7,8,9 hyl] phenylmethyl]-5-methyl-cylopent[4,5]imidao[2, 1-b]purin-49(3H)one (SCH51866) with an IC50 of 1.55 microM. This new phosphodiesterase is highly specific for cGMP. Its Km of approximately 0.07 microM for cGMP is the lowest yet reported for a PDE, being at least 40-170 times lower than that of PDE5 and PDE6, respectively.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

June 19, 1998

Volume

273

Issue

25

Start / End Page

15553 / 15558

Location

United States

Related Subject Headings

  • Phosphodiesterase Inhibitors
  • Molecular Weight
  • Molecular Sequence Data
  • Kinetics
  • Imidazoles
  • Gene Expression
  • Databases, Factual
  • Cyclic GMP
  • Cloning, Molecular
  • COS Cells
 

Citation

APA
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ICMJE
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Soderling, S. H., Bayuga, S. J., & Beavo, J. A. (1998). Identification and characterization of a novel family of cyclic nucleotide phosphodiesterases. J Biol Chem, 273(25), 15553–15558. https://doi.org/10.1074/jbc.273.25.15553
Soderling, S. H., S. J. Bayuga, and J. A. Beavo. “Identification and characterization of a novel family of cyclic nucleotide phosphodiesterases.J Biol Chem 273, no. 25 (June 19, 1998): 15553–58. https://doi.org/10.1074/jbc.273.25.15553.
Soderling SH, Bayuga SJ, Beavo JA. Identification and characterization of a novel family of cyclic nucleotide phosphodiesterases. J Biol Chem. 1998 Jun 19;273(25):15553–8.
Soderling, S. H., et al. “Identification and characterization of a novel family of cyclic nucleotide phosphodiesterases.J Biol Chem, vol. 273, no. 25, June 1998, pp. 15553–58. Pubmed, doi:10.1074/jbc.273.25.15553.
Soderling SH, Bayuga SJ, Beavo JA. Identification and characterization of a novel family of cyclic nucleotide phosphodiesterases. J Biol Chem. 1998 Jun 19;273(25):15553–15558.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

June 19, 1998

Volume

273

Issue

25

Start / End Page

15553 / 15558

Location

United States

Related Subject Headings

  • Phosphodiesterase Inhibitors
  • Molecular Weight
  • Molecular Sequence Data
  • Kinetics
  • Imidazoles
  • Gene Expression
  • Databases, Factual
  • Cyclic GMP
  • Cloning, Molecular
  • COS Cells