title: L-canavanine is a time-controlled mechanism-based inhibitor of Pseudomonas aeruginosa arginine deiminase.
abstract: The mechanism for inhibition of the Pseudomonas aeruginosa arginine deiminase (PaADI) by the arginine analogue l-canavanine was investigated. Inhibition by this substance (kinact = 0.31 +/- 0.03 min-1 and Ki = 1.7 +/- 0.5 mM) is associated with the formation of a modestly stable S-alkylthiouronium intermediate, detected by using kinetic techniques and identified by using electrospray ionization mass spectrometry. The electronic and/or orientation effects, caused by oxygen-for-methylene substitution in l-canavanine, on the rate of enzyme regeneration from the S-alkylthiouronium intermediate could serve as the basis for a strategy for the rational design of new slow substrate inhibitors of ADI.
authors.affiliation: Department of Chemistry, University of New Mexico, Albuquerque, New Mexico 87131, USA.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Lu
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Feng
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.forename: Debra
authors.initials: D
authors.lastname: Dunaway-Mariano
authors.forename: John R
authors.initials: JR
authors.lastname: Engen
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Mariano
mesh_terms: D001120:Arginine / Q000737:chemistry; D002172:Canavanine / Q000737:chemistry* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006867:Hydrolases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D015394:Molecular Structure; D011550:Pseudomonas aeruginosa / Q000201:enzymology*; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D002172:Canavanine; D001120:Arginine; D006867:Hydrolases; C019723:arginine deiminase