Hsc70 ATPase: An insight into water dissociation and joint catalytic role of K+ and Mg2+ metal cations in the hydrolysis reaction

Mauro Boero*, Takashi Ikeda, Etsuro Ito, Kiyoyuki Terakura

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

55 Citations (Scopus)


Hybrid quantum mechanics/molecular mechanics simulations, coupled to the recently introduced metadynamics method, performed on the adenosine triphosphate (ATP) of the bovine Hsc70 ATPase protein, show which specific water molecule of the solvation shell of the Mg2+ metal cation acts as a trigger in the initial phase of the ATP hydrolysis reaction in ATP synthase. Furthermore, we provide a detailed picture of the reaction mechanism, not accessible to experimental probes, that allows us to address two important issues not yet unraveled: (i) the pathway followed by a proton and a hydroxyl anion, produced upon dissociation of a putative catalytic H2O molecule, that is crucial in the selection of the reaction channel leading to the hydrolysis; (ii) the unique and cooperative role of K+ and Mg2+ metal ions in the reaction, acting as cocatalysts and promoting the release of the inorganic phosphate via an exchange of the OH- hydroxyl anion between their respective solvation shells. This is deeply different from the proton wire mechanism evidenced, for instance, in actin and lowers significantly the free energy barrier of the reaction.

Original languageEnglish
Pages (from-to)16798-16807
Number of pages10
JournalJournal of the American Chemical Society
Issue number51
Publication statusPublished - 2006 Dec 27
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry


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