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Two GAF (for cGMP binding and stimulated PDEs,\n                    <jats:italic>Anabaena a<\/jats:italic>\n                    denylyl cyclases, and\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    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\n                    <jats:italic>Dictyostelium discoideum<\/jats:italic>\n                    RegA, and a probable PDE from\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    . It is most similar to the\n                    <jats:italic>T. brucei<\/jats:italic>\n                    PDE2A (89% identity). TbPDE2B has substrate specificity for cAMP with a\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>m<\/jats:sub>\n                    of 2.4 \u03bcM. 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 selective for the mammalian PDE families 2, 3, 5, and 6 (erythro-9-[3-(2-hydroxynonyl)]-adenine, enoximone, zaprinast, and sildenafil) were also unable to inhibit this enzyme. However, dipyridamole was a reasonably good inhibitor of this enzyme with an IC\n                    <jats:sub>50<\/jats:sub>\n                    of 27 \u03bcM. cAMP plays key roles in cell growth and differentiation in this parasite, and PDEs are responsible for the hydrolysis of this important second messenger. Therefore, parasite PDEs, including this one, have the potential to be attractive targets for selective drug design.\n                  <\/jats:p>","DOI":"10.1073\/pnas.002031599","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:37:36Z","timestamp":1027679856000},"page":"4714-4719","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":47,"title":["Cloning and characterization of a cAMP-specific phosphodiesterase (TbPDE2B) from\n                    <i>Trypanosoma brucei<\/i>"],"prefix":"10.1073","volume":"99","author":[{"given":"Ana","family":"Rasc\u00f3n","sequence":"first","affiliation":[{"name":"Instituto de Biolog\u00eda Experimental, Universidad Central de Venezuela, Apartado 47.069, Caracas 1041-A, Venezuela; and Department of Pharmacology, Box 357280, University of Washington, Seattle, WA 98195-7280"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott 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