Cloning and characterization of a cAMP-specific phosphodiesterase (TbPDE2B) from Trypanosoma brucei

Proceedings of the National Academy of Sciences of the United States of America
Ana RascónJ A Beavo

Abstract

Here we report the cloning, expression, and characterization of a cAMP-specific phosphodiesterase (PDE) from Trypanosoma brucei (TbPDE2B). Using a bioinformatic approach, two different expressed sequence tag clones were identified and used to isolate the complete sequence of two identical PDE genes arranged in tandem. Each gene consists of 2,793 bases that predict a protein of 930 aa with a molecular mass of 103.2 kDa. Two GAF (for cGMP binding and stimulated PDEs, Anabaena adenylyl cyclases, and Escherichia coli FhlA) domains, similar to those contained in many signaling molecules including mammalian PDE2, PDE5, PDE6, PDE10, and PDE11, were located N-terminal to a consensus PDE catalytic domain. The catalytic domain is homologous to the catalytic domain of all 11 mammalian PDEs, the Dictyostelium discoideum RegA, and a probable PDE from Caenorhabditis elegans. It is most similar to the T. brucei PDE2A (89% identity). TbPDE2B has substrate specificity for cAMP with a K(m) of 2.4 microM. cGMP is not hydrolyzed by TbPDE2B nor does this cyclic nucleotide modulate cAMP PDE activity. The nonselective PDE inhibitors 3-isobutyl-1-methylxanthine, papaverine and pentoxifyline are poor inhibitors of TbPDE2B. Similarly, PDE inhibitors sel...Continue Reading

References

Jan 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·H CharbonneauJ A Beavo
Apr 1, 1990·Trends in Pharmacological Sciences·J A Beavo, D H Reifsnyder
Oct 5, 1990·Journal of Molecular Biology·S F AltschulD J Lipman
Aug 1, 1988·Experimental Parasitology·M Gonzales-PerdomoS Goldenberg
Mar 1, 1985·Infection·H Knothe, G A Dette
Sep 1, 1985·Infection and Immunity·S L ReedC E Davis
Nov 1, 1985·Molecular and Biochemical Parasitology·M T Téllez-IñónH N Torres
Feb 1, 1988·Pharmacology, Biochemistry, and Behavior·M Williams, M F Jarvis
Nov 1, 1974·Hoppe-Seyler's Zeitschrift für physiologische Chemie·R D Walter
Apr 1, 1980·Molecular and Biochemical Parasitology·M F GonçalvesW Colli
May 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·R S Hansen, J A Beavo
Dec 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·R PillaiJ Colicelli
May 24, 1994·Proceedings of the National Academy of Sciences of the United States of America·R H CoteV Y Arshavsky
Nov 1, 1993·Trends in Biochemical Sciences·W R Engels
Jan 20, 1998·Trends in Biochemical Sciences·L Aravind, C P Ponting
Mar 13, 1998·Molecular and Biochemical Parasitology·B ReunerM Boshart
Apr 18, 1998·Methods : a Companion to Methods in Enzymology·J M Atienza, J Colicelli
May 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·J SchultzC P Ponting
Dec 11, 1999·Nucleic Acids Research·A BatemanE L Sonnhammer
Mar 14, 2000·Current Opinion in Cell Biology·S H Soderling, J A Beavo
May 4, 2001·International Journal for Parasitology·T SeebeckR Zoraghi
Jun 1, 1995·Parasitology Today·S V Graham

❮ Previous
Next ❯

Citations

Mar 15, 2005·Cellular Signalling·Tasmina A Goraya, Dermot M F Cooper
Mar 21, 2002·Il Farmaco·Piaz Vittorio DalM C Castellana
Jan 20, 2004·European Journal of Biochemistry·Stefan KunzMichael Boshart
Mar 9, 2006·BMC Microbiology·Andrea JohnerThomas Seebeck
Aug 24, 2011·Future Medicinal Chemistry·Michael P Pollastri, Robert K Campbell
Dec 5, 2006·Proceedings of the National Academy of Sciences of the United States of America·Sunil LaxmanJoseph A Beavo
Dec 13, 2005·The FEBS Journal·Stefan KunzThomas Seebeck
Nov 11, 2005·Molecular and Biochemical Parasitology·Stefan KunzThomas Seebeck
Jan 13, 2011·FEMS Microbiology Reviews·Matthew K Gould, Harry P de Koning
Apr 19, 2012·Acta Microbiologica Et Immunologica Hungarica·Bibi Sedigheh Fazly BazzazHossein Hosseinzadeh
Apr 24, 2007·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Matthew J O'ShaughnessyBruce R Blazar
Oct 18, 2005·Molecular and Biochemical Parasitology·Guillermo D AlonsoMirtha M Flawiá
Apr 30, 2015·MBio·Michael OberholzerKent L Hill
Dec 7, 2005·The Journal of Biological Chemistry·Marco Gross-LangenhoffJoachim E Schultz
Dec 15, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Michael OberholzerThomas Seebeck
Dec 17, 2008·Molecular BioSystems·Najl V ValeyevDeclan G Bates
Jan 27, 2004·Molecular Pharmacology·Roya ZoraghiSharron H Francis
Nov 26, 2004·The Journal of Biological Chemistry·Sunil LaxmanJoseph A Beavo

❮ Previous
Next ❯

Related Concepts

Related Feeds

African Trypanosomiasis

African trypanosomiasis, also known as sleeping sickness, is an insect-borne parasitic disease of humans and other animals. It is caused by protozoa of the species Trypanosoma brucei and almost invariably progresses to death unless treated. Discover the latest research on African trypanosomiasis here.