title: Phospholipase A2 from Trypanosoma brucei gambiense and Trypanosoma brucei brucei: inhibition by organotins.
abstract: Activity and kinetics of phospholipase A2 (PLA2) from Trypanosoma brucei gambiense (Wellcome strain) and Trypanosoma brucei brucei (GUTat 3.1) were examined using two different fluorescent substrates. The activity in the supernatants of sonicated parasites was Ca2+-independent, strongly stimulated by Triton X-100 with optimum activity at 37 degrees C and pH 6.5-8.5. To encourage a possible interaction between the parasite enzyme and organotin compounds, fatty acid derivatives of dibutyltin dichloride were synthesized and evaluated as potential inhibitors of PLA2. The enzyme from the two-trypanosome species differ with respect to kinetic parameters and are noncompetitively inhibited by the organotin compounds. The Michaelis constant (KM) for PLA2 from T. b. brucei is 63.87 and 30.90 microM while for T. b. gambiense it is 119.64 and 32.91 microM for the substrates 1,2-bis-(1-pyrenebutanoyl)-sn-glycero-3-phosphocholine (PBGPC) and 2-(12-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)dodecanoyl-1-hexadecanoyl-sn-glycero-3-phosphocholine (NBDC12-HPC), respectively.
authors.affiliation: Protozoology Department, Institute of Tropical Medicine, Nagasaki University, Japan.
authors.forename: M N
authors.initials: MN
authors.lastname: Shuaibu
authors.forename: H
authors.initials: H
authors.lastname: Kanbara
authors.forename: T
authors.initials: T
authors.lastname: Yanagi
authors.forename: D A
authors.initials: DA
authors.lastname: Ameh
authors.forename: J J
authors.initials: JJ
authors.lastname: Bonire
authors.forename: A J
authors.initials: AJ
authors.lastname: Nok
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D017830:Octoxynol / Q000494:pharmacology; D009947:Organotin Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054467:Phospholipases A2; D013379:Substrate Specificity; D013696:Temperature; D014344:Trypanocidal Agents / Q000737:chemistry / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects / Q000201:enzymology*; D014347:Trypanosoma brucei gambiense / Q000187:drug effects / Q000201:enzymology*
chemical_list: D005227:Fatty Acids; D009947:Organotin Compounds; D014344:Trypanocidal Agents; D017830:Octoxynol; D010741:Phospholipases A; D054467:Phospholipases A2; C020735:dibutyldichlorotin; D002118:Calcium