HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 276, Issue 15, 11559-11566, April 13, 2001

This Article Full Text Full Text (PDF) All Versions of this Article: 276/15/11559    most recent M005419200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zoraghi, R. Articles by Seebeck, T. Search for Related Content PubMed PubMed Citation Articles by Zoraghi, R. Articles by Seebeck, T. Social Bookmarking                      What's this?

Characterization of TbPDE2A, a Novel Cyclic Nucleotide-specific Phosphodiesterase from the Protozoan Parasite Trypanosoma brucei^*

Roya Zoraghi, Stefan Kunz, Kewei Gong^§, and Thomas Seebeck^¶

From the Institute for Cell Biology, University of Bern, Baltzerstrasse 4, Berne CH-3012, Switzerland

This study reports the identification and characterization of a cAMP-specific phosphodiesterase from the parasitic hemoflagellate Trypanosoma brucei. TbPDE2A is a class I phosphodiesterase. Its catalytic domain exhibits 30-40% sequence identity with those of all 11 mammalian phosphodiesterase (PDE) families, as well as with PDE2 from Saccharomyces cerevisiae, dunce from Drosophila melanogaster, and regA from Dictyostelium discoideum. The overall structure of TbPDE2A resembles that of human PDE11A in that its N-terminal region contains a single GAF domain. This domain is very similar to those of the mammalian PDE2, -5, -6, -10, and -11, where it constitutes a potential cGMP binding site. TbPDE2A can be expressed in S. cerevisiae, and it complements an S. cerevisiae PDE deletion strain. Recombinant TbPDE2A is specific for cAMP, with a K_m of ~2 µM. It is entirely resistant to the nonselective PDE inhibitor 3-isobutyl-1-methylxanthine, but it is sensitive to trequinsin, dipyridamole, sildenafil, and ethaverine with IC₅₀ values of 5.4, 5.9, 9.4, and 14.2 µM, respectively. All four compounds inhibit proliferation of bloodstream form trypanosomes in culture, indicating that TbPDE2A is an essential enzyme.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EMBL Data Bank with accession number(s) AF263280.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				S. Laxman and J. A. Beavo Cyclic Nucleotide Signaling Mechanisms in Trypanosomes: Possible Targets for Therapeutic Agents Mol. Interv., August 1, 2007; 7(4): 203 - 215. [Abstract] [Full Text] [PDF]

				S. Laxman, A. Rascon, and J. A. Beavo Trypanosome Cyclic Nucleotide Phosphodiesterase 2B Binds cAMP through Its GAF-A Domain J. Biol. Chem., February 4, 2005; 280(5): 3771 - 3779. [Abstract] [Full Text] [PDF]

				R. Zoraghi and T. Seebeck From the Cover: The cAMP-specific phosphodiesterase TbPDE2C is an essential enzyme in bloodstream form Trypanosoma brucei PNAS, April 2, 2002; 99(7): 4343 - 4348. [Abstract] [Full Text] [PDF]

				A. Rascon, S. H. Soderling, J. B. Schaefer, and J. A. Beavo Cloning and characterization of a cAMP-specific phosphodiesterase (TbPDE2B) from Trypanosoma brucei PNAS, April 2, 2002; 99(7): 4714 - 4719. [Abstract] [Full Text] [PDF]