A FYVE-containing unusual cyclic nucleotide phosphodiesterase from Trypanosoma cruzi.
Cyclic-nucleotide-specific phosphodiesterases (PDEs) are key players in the intracellular signaling pathways of the important human pathogen Trypanosoma cruzi. We report herein the identification of an unusual PDE from this protozoal organism. This enzyme, TcrPDEC, is a member of the class I PDEs, as determined from the presence of a characteristic signature sequence and from the conservation of a number of functionally important amino acid residues within its catalytic domain. Class I PDEs include a large number of PDEs from eukaryotes, among them all 11 human PDE families. Unusually for an enzyme of this class, TcrPDEC contains a FYVE-type domain in its N-terminal region, followed by two closely spaced coiled-coil domains. Its catalytic domain is located in the middle of the polypeptide chain, whereas all other class I enzymes contain their catalytic domains in their C-terminal parts. TcrPDEC can complement a PDE-deficient yeast strain. Unexpectedly for a kinetoplastid PDE, TcrPDEC is a dual-specificity PDE that accepts both cAMP and cGMP as its substrates.
Kunz
Stefan
S
Institute of Cell Biology, University of Bern, Bern, Switzerland.
Oberholzer
Michael
M
Seebeck
Thomas
T
D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D017124:Conserved Sequence; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D008969:Molecular Sequence Data; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins; D013379:Substrate Specificity; D014349:Trypanosoma cruzi / Q000201:enzymology*
D015800:Protozoan Proteins; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D006152:Cyclic GMP