Anticocaine catalytic antibodies

Deng, Shi Xian; Prada, Paloma de; Landry, Donald W.

doi:10.1016/s0022-1759(02)00237-5

Cited by 44 publications

(35 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[1][2][3][4]6 An alternative approach is to interfere with the delivery of cocaine to its receptors or accelerate its metabolism in the body. 4,[7][8][9][10][11][12][13][14][15][16][17] Butyrylcholinesterase (BChE), the principal plasma enzyme that catalyzes cocaine hydrolysis into its biologically inactive metabolites, is an ideal target for this purpose. There are some clear advantages of using this enzyme to accelerate the cocaine metabolism.…”

Section: Introductionmentioning

confidence: 99%

Free Energy Perturbation (FEP) Simulation on the Transition States of Cocaine Hydrolysis Catalyzed by Human Butyrylcholinesterase and Its Mutants

et al. 2007

View full text Add to dashboard Cite

A novel computational protocol based on free energy perturbation (FEP) simulations on both the free enzyme and transition state structures has been developed and tested to predict the mutation-caused shift of the free energy change from the free enzyme to the rate-determining transition state for human butyrylcholinesterase (BChE)-catalyzed hydrolysis of (-)-cocaine. The calculated shift, denoted by ΔΔG(1→2), of such kind of free energy change determines the catalytic efficiency (k cat /K M ) change caused by the simulated mutation transforming enzyme 1 to enzyme 2. By using the FEP-based computational protocol, the ΔΔG(1→2) values for the mutations A328W/Y332A → A328W/Y332G and A328W/Y332G → A328W/Y332G/A199S were calculated to be -0.22 and -1.94 kcal/mol, respectively. The calculated ΔΔG(1→2) values predict that the change from the A328W/Y332A mutant to the A328W/Y332G mutant should slightly improve the catalytic efficiency and that the change from the A328W/Y332G mutant to the A328W/Y332G/A199S mutant should significantly improve the catalytic efficiency of the enzyme for the (-)-cocaine hydrolysis. The predicted catalytic efficiency increases are supported by the experimental data showing that k cat /K M = 8.5 × 10 6 , 1.4 × 10 7 , and 7.2 × 10 7 min -1 M -1 for the A328W/Y332A, A328W/Y332G, and A328W/Y332G/A199S mutants, respectively. The qualitative agreement between the computational and experimental data suggests that the FEP simulations may provide a promising protocol for rational design of highactivity mutants of an enzyme. The general computational strategy of the FEP simulation on a transition state can be used to study the effects of a mutation on the activation free energy for any enzymatic reaction.

show abstract

Section: Introductionmentioning

confidence: 99%

Free Energy Perturbation (FEP) Simulation on the Transition States of Cocaine Hydrolysis Catalyzed by Human Butyrylcholinesterase and Its Mutants

et al. 2007

View full text Add to dashboard Cite

show abstract

“…mAb 15A10 is reported to decrease intravenous cocaine self-administration but to not suppress food-maintained response in rats (Baird et al, 2000). In addition, the catalytic antibody offered some protective effect against cocaine-induced lethality and hypertension for low doses of cocaine in catecholamine-sensitized rats (Mets et al, 1998;Deng et al, 2002). However, these effects were observed only This research was supported by United States Public Health Service grant DA021416-01.…”

mentioning

confidence: 99%

Rapid and Robust Protection against Cocaine-Induced Lethality in Rats by the Bacterial Cocaine Esterase

Cooper¹,

Narasimhan²,

Sunahara³

et al. 2006

Mol Pharmacol

View full text Add to dashboard Cite

“…CocE is a globular, 574-amino acid enzyme with a molecular mass of ϳ65 kDa and is the most efficient protein catalyst for the hydrolysis of cocaine characterized to date (Bresler et al, 2000;Larsen et al, 2002;Turner et al, 2002;Rogers et al, 2005). The hydrolytic rate constant of this enzyme (k cat /K m ) is 1000-fold higher than that of BChE and 10 5 -and 10 6 -fold faster than catalytic antibodies such as monoclonal antibody 15A10 (Deng et al, 2002;Turner et al, 2002). A recent in vivo study in rats has further demonstrated CocE's superior catalytic efficiency and selectivity for cocaine compared with BChE (Cooper et al, 2006).…”

mentioning

confidence: 99%