Abstract
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 language | English |
|---|---|
| Pages (from-to) | 16798-16807 |
| Number of pages | 10 |
| Journal | Journal of the American Chemical Society |
| Volume | 128 |
| Issue number | 51 |
| DOIs | |
| Publication status | Published - 2006 Dec 27 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Chemistry(all)
Cite this
Hsc70 ATPase : An insight into water dissociation and joint catalytic role of K+ and Mg2+ metal cations in the hydrolysis reaction. / Boero, Mauro; Ikeda, Takashi; Ito, Etsuro; Terakura, Kiyoyuki.
In: Journal of the American Chemical Society, Vol. 128, No. 51, 27.12.2006, p. 16798-16807.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Hsc70 ATPase
T2 - An insight into water dissociation and joint catalytic role of K+ and Mg2+ metal cations in the hydrolysis reaction
AU - Boero, Mauro
AU - Ikeda, Takashi
AU - Ito, Etsuro
AU - Terakura, Kiyoyuki
PY - 2006/12/27
Y1 - 2006/12/27
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=33845922101&partnerID=8YFLogxK
U2 - 10.1021/ja064117k
DO - 10.1021/ja064117k
M3 - Article
C2 - 17177430
AN - SCOPUS:33845922101
VL - 128
SP - 16798
EP - 16807
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 51
ER -