Reaction mechanism and free energy profile for acylation of Candida Antarctica lipase B with methylcaprylate and acetylcholine: Density functional theory calculations

Googheri, Mohammad Sadegh Sadeghi; Housaindokht, Mohammad Reza; Sabzyan, Hassan

doi:10.1016/j.jmgm.2014.10.001

Cited by 12 publications

(5 citation statements)

References 38 publications

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“…4A, the protein RMSD values from representative trajectories for each system reveal a similar flexibility of GLCM in the presence of amylotriose substrates. This observation aligns with previous findings across various systems, encompassing glycoside hydrolases and other enzymes [33–36].…”

Section: Resultssupporting

confidence: 92%

Ultrasound-Assisted Hydrolysis of Food Waste using Glucoamylase: Statistical Optimization and Mechanistic Analysis with Molecular Simulations

Anand,

Kumar,

Khaire

et al. 2023

Preprint

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Food waste represents a promising and cost-effective resource for synthesizing value-added products through a fermentative pathway. Preceding fermentation, the hydrolysis of food waste into monomeric sugars is a crucial step. This study presents a comprehensive investigation of food waste hydrolysis, encompassing experimental and computational approaches, using glucoamylase (GLCM) enzyme. Initial optimization of hydrolysis parameters was conducted through the Box–Behnken design of experiments, resulting in a total reducing sugar yield (TRS) of 263.4 mg/g biomass under optimized conditions within 42 hours. Sonication of hydrolysis mixture at 35 kHz at 20% duty cycle, yielded a 4× reduction in hydrolysis time with 22% enhancement in TRS yield (320 mg/g biomass). Analysis of GLCM’s secondary structure revealed sonication-induced changes through FTIR spectra deconvolution in both control and test experiments. Sonication led to a reduction in α-helix content and an increase in random coil content. Molecular dynamics simulations, including molecular docking, unveiled the majority of amino acid residues associated with the GLCM binding pocket in the α-helix and random coil regions. Consequently, sonication widened the binding pockets, facilitating easier transport of substrate and product. This effect translated into improved reaction kinetics in food waste hydrolysis.Research HighlightsStatistical optimization of food waste hydrolysis: TRS yield = 263.4 mg/g in 42 h4x reduction of hydrolysis time, 22% rise in TRS yield with 35 kHz sonicationSonication reduced α-helix content & increased random coil content of glucoamylaseMolecular docking simulation to deduce mechanism of ultrasound-assisted hydrolysisMD simulations reveal widening of binding pockets and enhancing catalytic efficiency

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Section: Resultssupporting

confidence: 92%

Ultrasound-Assisted Hydrolysis of Food Waste using Glucoamylase: Statistical Optimization and Mechanistic Analysis with Molecular Simulations

Anand,

Kumar,

Khaire

et al. 2023

Preprint

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“…The acylation reaction catalyzed by C. antarctica lipase B in aqueous solution was examined with DFT, specifically using B3PW91, by Sadeghi Googheri et al with methyl caprylate and acetylcholine as substrates . The computed free-energy barriers for the two acylation steps for methyl caprylate are 9.2 and 7.9 kcal/mol, respectively.…”

Section: Carboxylic Ester Bond Hydrolysismentioning

confidence: 99%

Computational Studies of Glycoside, Carboxylic Ester, and Thioester Hydrolase Mechanisms: A Review

Reilly

Rovira

2015

Ind. Eng. Chem. Res.

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This article is a review of computational work over the last ∼15 years to elucidate the catalytic mechanisms of three major enzyme classes: glycoside hydrolases, carboxylic ester hydrolases, and thioesterases. The mechanisms of glycoside hydrolases that both invert and retain the configuration of the anomeric carbon atom of the labile glycosidic bond are covered, as is the twisting of the glycosidic bond exerted by members of different glycoside hydrolase families. The hydrolytic mechanisms and substrate binding of five different carboxylic ester hydrolase classesacetylcholinesterases, butyrylcholinesterases, cocaine esterases, carboxylesterases, and triacylglycerol lipasesare addressed. Finally, the mechanism of members of a thioesterase family with HotDog tertiary structures is covered.

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“…Goegheri et al used DFT calculations to study the hydrolysis of two esters, namely, acetylcholine and methylcaprylate, by Candida Antarctica lipase B (CALB). 20 It was shown that the oxyanion intermediates are stabilized by the surrounding residues.…”

Section: Introductionmentioning

confidence: 99%

“…It was reported that the acylation (Steps 1 and 2 in Figure ) and deacylation (Steps 3 and 4 in Figure ) processes proceeded in four steps involving tetrahedral oxyanion intermediates. Goegheri et al used DFT calculations to study the hydrolysis of two esters, namely, acetylcholine and methylcaprylate, by Candida Antarctica lipase B (CALB) . It was shown that the oxyanion intermediates are stabilized by the surrounding residues.…”

Section: Introductionmentioning

confidence: 99%

Computational Analysis of the Inhibition Mechanism of NOTUM by the ONIOM Method

Yildiz

2022

ACS Omega

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Notum is a member of serine hydrolyses that cleaves the palmitoleate moiety from Wingless-related integration site (Wnt) ligands. This enzyme plays crucial functions through modulating the Wnt signaling pathway. Inhibition of Notum carries therapeutic effects against a number of maladies including osteoporosis, cancer, and Alzheimer’s disease. Recently, a class of irreversible inhibitors based on esters of 4-(indolin-1-yl)-4-oxobutanoic acid have been reported. Using the crystal structures of enzyme-4-(indolin-1-yl)-4-oxobutanoate adduct and 4-(indolin-1-yl)-4-oxobutanoic acid-enzyme complex, we studied computationally the proposed inhibition mechanism using model systems based on the own n-layered integrated molecular orbital and molecular mechanics (ONIOM) method. In the first place, model systems were formulated to investigate the transesterification between the catalytic serine residue, Ser-232, and the methyl ester of 4-(indolin-1-yl)-4-oxobutanoate. In the second place, the hydrolysis mechanism of the resultant enzyme–inhibitor adduct was studied. The energetics of these steps were analyzed using a density functional theory functional in the ONIOM method. In addition, the roles of active-site residues during these steps were highlighted. It was found that the hydrolysis of the covalent adduct is highly endergonic corroborating the irreversible inhibition mechanism. These results will shed light not only on the inhibition mechanism but also on the catalytic mechanism.

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Reaction mechanism and free energy profile for acylation of Candida Antarctica lipase B with methylcaprylate and acetylcholine: Density functional theory calculations

Cited by 12 publications

References 38 publications

Ultrasound-Assisted Hydrolysis of Food Waste using Glucoamylase: Statistical Optimization and Mechanistic Analysis with Molecular Simulations

Ultrasound-Assisted Hydrolysis of Food Waste using Glucoamylase: Statistical Optimization and Mechanistic Analysis with Molecular Simulations

Computational Studies of Glycoside, Carboxylic Ester, and Thioester Hydrolase Mechanisms: A Review

Computational Analysis of the Inhibition Mechanism of NOTUM by the ONIOM Method

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