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Updated: Jun 19, 2026

Isotopic Effect in Double Proton Transfer Process of Porphycene Investigated by Enhanced QM/MM Method
Published on: July 19, 2019
Mechanism and plasticity of isochorismate pyruvate lyase: a computational study
Sergio Martí1, Juan Andrés, Vicent Moliner
1Departament de Quimica Fisica i Analitica, Universitat Jaume I, 12071 Castellon, Spain.
Abstract:
The isochorismate pyruvate lyase (IPL) from Pseudomonas aeruginosa, designated as PchB, catalyzes the transformation of isochorismate into pyruvate and salicylate, but it also catalyzes the rearrangement of chorismate into prephenate, suggesting that both reactions may proceed by a pericyclic mechanism. In this work, molecular dynamics simulations employing hybrid quantum mechanics/molecular mechanics methods have been carried out to get a detailed knowledge of the reaction mechanism of PchB. The results provide a theoretical rate constant enhancement by comparison with the reaction in solution, in agreement with the experimental data, and confirm the pericyclic nature of the reaction mechanism. The robustness of this promiscuous enzyme has been checked by considering the impact of Ala37Ile mutation, previously proposed by us to improve the secondary chorismate mutase (CM) activity. The effect of this mutation, which was shown to increase the rate constant for the CM activity by a factor of 10(3), also increases the IPL catalytic efficiency, although only by a factor of 6.
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