Understanding the different activities of highly promiscuous MbtI by computational methods

Silvia Ferrer, Sergio Martí, Vicent Moliner, Iñaki Tuñón, Juan Bertrán

    Research output: Contribution to journalArticleResearchpeer-review

    15 Citations (Scopus)


    Salicylate synthase from Mycobacterium tuberculosis, MbtI, is a highly promiscuous Mg 2+ dependent enzyme with up to four distinct activities detected in vitro: isochorismate synthase (IS), isochorismate pyruvate lyase (IPL), salicylate synthase (SS) and chorismate mutase (CM). In this paper, Molecular Dynamic (MD) simulations employing hybrid quantum mechanics/molecular mechanics (QM/MM) potentials have been carried out to get a detailed knowledge of the IS and the IPL activities at the molecular level. According to our simulations, the architecture of the MbtI active site allows catalyzing the two reactions: the isochorismate formation, by means of a stepwise mechanism, and the salicylate production from isochorismate, that appears to be pericyclic in nature. Findings also explain the role of the magnesium cation and the pH dependence activity experimentally observed in MbtI. Mg 2+ would be polarizing and pre-organizing the substrate and active site, as well as shifting the pK a values of key active site residues. © the Owner Societies 2012.
    Original languageEnglish
    Pages (from-to)3482-3489
    JournalPhysical Chemistry Chemical Physics
    Issue number10
    Publication statusPublished - 14 Mar 2012


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