title: Inhibition of (+)-aristolochene synthase with iminium salts resembling eudesmane cation.
abstract: Trigonal iminium halides of (4aS,7S)-1,4a-dimethyl- and (4aS,7S)-4a-methyl-7-(prop-1-en-2-yl)-2,3,4,4a,5,6,7,8-octahydroquinolinium ions, aimed to mimic transition states associated with the aristolochene synthase-catalyzed cyclization of (-)-germacrene A to eudesmane cation, were evaluated under standard kinetic steady-state conditions. In the presence of inorganic diphosphate, these analogues were shown to competitively inhibit the enzyme, suggesting a stabilizing role for the diphosphate leaving group in this apparently endothermic transformation.
authors.affiliation: School of Chemistry, Cardiff University, Cardiff, United Kingdom.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Faraldos
authors.forename: Rudolf K
authors.initials: RK
authors.lastname: Allemann
mesh_terms: D001230:Aspergillus / Q000201:enzymology; D002384:Catalysis; D003500:Cyclization; D007097:Imines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007535:Isomerases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D010407:Penicillium / Q000201:enzymology; D012492:Salts; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D045787:Sesquiterpenes, Eudesmane / Q000737:chemistry*; D045788:Sesquiterpenes, Germacrane / Q000737:chemistry*; D013237:Stereoisomerism; D014026:Nicotiana / Q000201:enzymology
chemical_list: D007097:Imines; D012492:Salts; D012717:Sesquiterpenes; D045787:Sesquiterpenes, Eudesmane; D045788:Sesquiterpenes, Germacrane; C054277:aristolochene; C471077:germacrene A; C015872:eudesmane; D007535:Isomerases; C060050:aristolochene synthase