title: Bacillus anthracis edema factor substrate specificity: evidence for new modes of action.
abstract: Since the isolation of Bacillus anthracis exotoxins in the 1960s, the detrimental activity of edema factor (EF) was considered as adenylyl cyclase activity only. Yet the catalytic site of EF was recently shown to accomplish cyclization of cytidine 5'-triphosphate, uridine 5'-triphosphate and inosine 5'-triphosphate, in addition to adenosine 5'-triphosphate. This review discusses the broad EF substrate specificity and possible implications of intracellular accumulation of cyclic cytidine 3':5'-monophosphate, cyclic uridine 3':5'-monophosphate and cyclic inosine 3':5'-monophosphate on cellular functions vital for host defense. In particular, cAMP-independent mechanisms of action of EF on host cell signaling via protein kinase A, protein kinase G, phosphodiesterases and CNG channels are discussed.
authors.affiliation: Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA. Mgoettl@emory.edu
authors.forename: Martin
authors.initials: M
authors.lastname: Göttle
authors.forename: Stefan
authors.initials: S
authors.lastname: Dove
authors.forename: Roland
authors.initials: R
authors.lastname: Seifert
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism* / Q000633:toxicity; D001408:Bacillus anthracis / Q000378:metabolism*; D001427:Bacterial Toxins / Q000378:metabolism* / Q000633:toxicity; D020134:Catalytic Domain; D005098:Exotoxins / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D009712:Nucleotides, Cyclic / Q000378:metabolism; D011487:Protein Conformation; D015398:Signal Transduction; D013379:Substrate Specificity; D014542:Uridine Monophosphate / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D005098:Exotoxins; D009712:Nucleotides, Cyclic; C030325:anthrax toxin; C045338:cyclic 3',5'-uridine monophosphate; D014542:Uridine Monophosphate; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000262:Adenylyl Cyclases