Effect of electrostatic interaction on the mechanism of dehalogenation catalyzed by haloalkane dehalogenase

Zhang, Yuhua; Chen, Dezhan; Zhang, Honghong; Liu, Jian-Biao; Mi, Shizhen; Zhang, Guiqiu

doi:10.1002/qua.22509

Cited by 1 publication

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References 40 publications

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“…34 The computational method, the basis set, and the relative parameters here have been successfully used to study the enzymatic reaction mechanism through quantum chemical model and the results are reasonable and reliable. [35][36][37][38][39][40][41][42][43][44]…”

Section: Quantum Chemical Calculationsmentioning

confidence: 99%

New insights into the mechanism of the Schiff base hydrolysis catalyzed by type I dehydroquinate dehydratase from S. enterica: a theoretical study

Yao

2012

Org. Biomol. Chem.

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The reaction pathway of Schiff base hydrolysis catalyzed by type I dehydroquinate dehydratase (DHQD) from S. enterica has been studied by performing molecular dynamics (MD) simulations and density functional theory (DFT) calculations and the corresponding potential energy profile has also been identified. On the basis of the results, the catalytic hydrolysis process for the wild-type enzyme consists of three major reaction steps, including nucleophilic attack on the carbon atom involved in the carbon-nitrogen double bond of the Schiff base intermediate by a water molecule, deprotonation of the His143 residue, and dissociation between the product and the Lys170 residue of the enzyme. The remarkable difference between this and the previously proposed reaction mechanism is that the second step here, absent in the previously proposed reaction mechanism, plays an important role in facilitating the reaction through a key proton transfer by the His143 residue, resulting in a lower energy barrier. Comparison with our recently reported results on the Schiff base formation and dehydration processes clearly shows that the Schiff base hydrolysis is rate-determining in the overall reaction catalyzed by type I DHQD, consistent with the experimental prediction, and the calculated energy barrier of ∼16.0 kcal mol(-1) is in good agreement with the experimentally derived activation free energy of ∼14.3 kcal mol(-1). When the imidazole group of His143 residue is missing, the Schiff base hydrolysis is initiated by a hydroxide ion in the solution, rather than a water molecule, and both the reaction mechanism and the kinetics of Schiff base hydrolysis have been remarkably changed, clearly elucidating the catalytic role of the His143 residue in the reaction. The new mechanistic insights obtained here will be valuable for the rational design of high-activity inhibitors of type I DHQD as non-toxic antimicrobials, anti-fungals, and herbicides.

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Section: Quantum Chemical Calculationsmentioning

confidence: 99%

New insights into the mechanism of the Schiff base hydrolysis catalyzed by type I dehydroquinate dehydratase from S. enterica: a theoretical study

Yao

2012

Org. Biomol. Chem.

View full text Add to dashboard Cite

show abstract

Effect of electrostatic interaction on the mechanism of dehalogenation catalyzed by haloalkane dehalogenase

Cited by 1 publication

References 40 publications

New insights into the mechanism of the Schiff base hydrolysis catalyzed by type I dehydroquinate dehydratase from S. enterica: a theoretical study

New insights into the mechanism of the Schiff base hydrolysis catalyzed by type I dehydroquinate dehydratase from S. enterica: a theoretical study

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