TAILIEUCHUNG - Báo cáo khóa học: TbPDE1, a novel class I phosphodiesterase of Trypanosoma brucei

Cyclic nucleotide specific phosphodiesterases (PDEs) are important components of all cAMP signalling networks. In humans, 11 different PDE families have been identified to date, all of which belong to the class I PDEs. Pharmaco-logically, theyhavebecome of great interest as targets for the development of drugs for a large variety of clinical condi-tions. PDEs in parasitic protozoa have not yet been exten-sively investigated, despite their potential as antiparasitic drug targets. | Eur. J. Biochem. 271 637-647 2004 FEBS 2004 doi TbPDEI a novel class I phosphodiesterase of Trypanosoma brucei Stefan Kunz1 Thomas Kloeckner2 Lars-Oliver Essen3 I Thomas Seebeck1 and Michael Boshart2 institute of Cell Biology University of Bern Switzerland department of Biology I University of Munich Germany 3 Max Planck Institute for Biochemistry Mariinsried Grrmany Cyclic nucleotide specific phosphodiesterases PDEs are important components of all cAMP signalling networks. In humans 11 different PDE families have been identified to date all of which belong to the class I PDEs. Pharmacologically they have become of great interest as targets for the development of drugs for a large variety of clinical conditions. PDEs in parasitic protozoa have not yet been extensively investigated despite their potential as antiparasitic drug targets. The current study presents the identification and characterization of a novel class I PDE from the parasitic protozoon Trypanosoma brucei the causative agent of human sleeping sickness. This enzyme TbPDE1 is encoded by a single-copy gene located on chromosome 10 and it functionally complements PDE-deficient strains of Sac-chaoomyces ceoevrsrae. Its C-terminal catalytic domain shares about 30 amino acid identity including all functionally important residues with the catalytic domains of human PDEs. A fragment of TbPDE1 containing the catalytic domain could be expressed in active form in Escherichia coli. The recombinant enzyme is specific for cAMP but exhibits a remarkably high Km of 600 M for this substrate. Keywords African trypanosomes cAMP signaling class I phosphodiesterase sleeping sickness. Cyclic AMP is involved in the regulation of numerous biological functions such as the control of metabolic pathways in eubacteria 1 differentiation and virulence in fungi 2 cell aggregation in Dicryosrelium 3 transduction of gustatory and olfactory signals 4 the control of rhythmic oscillations in heart and .

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