title: Catalytic irreversible inhibition of bacterial and plant arginine decarboxylase activities by novel substrate and product analogues.
abstract: Arginine decarboxylase (ADC) activity from Escherichia coli and two plant species (oats and barley) was inhibited by five new substrate (arginine) and product (agmatine) analogues. The five compounds, (E)-alpha-monofluoromethyldehydroarginine (delta-MFMA), alpha-monofluoromethylarginine (MFMA), alpha-monofluoromethylagatine (FMA), alpha-ethynylagmatine (EA) and alpha-allenylagmatine (AA), were all more potent inhibitors of ADC activity than was alpha-difluoromethylarginine (DFMA), the only irreversible inhibitor of this enzyme described previously. The inhibition caused by the five compounds was apparently enzyme-activated and irreversible, since the loss of enzyme activity followed pseudo-first-order kinetics, was time-dependent, the natural substrate of ADC (arginine) blocked the effects of the inhibitors, and the inhibition remained after chromatography of inhibited ADC on Sephadex G-25 or on overnight dialysis of the enzyme. DFMA, FMA, delta-MFMA and MFMA were effective at very low concentrations (10 nM-10 microM) at inhibiting ADC activity in growing E. coli. FMA was also shown to deplete putrescine effectively in E. coli, particularly when combined with an inhibitor of ornithine decarboxylase, alpha-monofluoromethyl-putrescine. The potential uses of the compounds for the study of the role of polyamine biosynthesis in bacteria and plants is discussed.
authors.forename: A J
authors.initials: AJ
authors.lastname: Bitonti
authors.forename: P J
authors.initials: PJ
authors.lastname: Casara
authors.forename: P P
authors.initials: PP
authors.lastname: McCann
authors.forename: P
authors.initials: P
authors.lastname: Bey
mesh_terms: D000376:Agmatine / Q000031:analogs & derivatives / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D002523:Edible Grain / Q000187:drug effects / Q000201:enzymology*; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology*; D001467:Hordeum / Q000187:drug effects / Q000201:enzymology; D011700:Putrescine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000376:Agmatine; C035578:alpha-monofluoromethylputrescine; D001120:Arginine; D002262:Carboxy-Lyases; C019722:arginine decarboxylase; D011700:Putrescine