Theoretical modeling of the reaction mechanism of phosphate monoester hydrolysis in alkaline phosphatase

Violeta López-Canut, Sergio Martí, Juan Bertrán, Vicente Moliner, Iñaki Tuñó

    Research output: Contribution to journalArticleResearchpeer-review

    38 Citations (Scopus)

    Abstract

    The reaction mechanism of phosphate monoester hydrolysis in alkaline phosphatase is analyzed by means of hybrid QM/MM simulations. A recently developed semiempirical Hamiltonian, AMl/d-PhoT, which takes into account the d orbitals on the phosphorus atom, has been employed. The reaction mechanism obtained is either associative or dissociative, depending on the size of the QM subsystem. The results are rationalized on the basis of the degree of charge transfer from the reacting fragments to the two zinc ions present in the active site, which has been observed to be dependent on whether or not metal atoms and their coordination spheres are included in the QM region. The description obtained using the largest QM region agrees with the picture obtained from experimental data. © 2009 American Chemical Society.
    Original languageEnglish
    Pages (from-to)7816-7824
    JournalJournal of Physical Chemistry B
    Volume113
    Issue number22
    DOIs
    Publication statusPublished - 4 Jun 2009

    Fingerprint Dive into the research topics of 'Theoretical modeling of the reaction mechanism of phosphate monoester hydrolysis in alkaline phosphatase'. Together they form a unique fingerprint.

    Cite this