Molecular Orbital Study of the Interaction between MgATP and the Myosin Motor Domain:  The Highest Occupied Molecular Orbitals Indicate the Reaction Site of ATP Hydrolysis

Kagawa, Hiroshi; Mori, Kazuhide

doi:10.1021/jp991117g

Cited by 17 publications

(24 citation statements)

References 14 publications

(29 reference statements)

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“…These approaches range from simple molecular orbital calculations to sophisticated quantum mechanical calculations of isolated active site of protein such as myosin [26,27,30,[32][33][34][35][36][37]. In the field of quantum chemistry, many investigations have been carried out at the Hartree Fock level.…”

Section: Resultsmentioning

confidence: 99%

Quantum chemical analysis of ATP, GTP and related compounds in gas phase

Pakiari

Farrokhnia

Moradshahi

2010

JICS

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Adenosine 5 ' -triphosphate (ATP) and Guanine 5 ' -triphosphate (GTP), which are highly significant species for biological system as sources of energy, along with two other compounds, ribose 5 ' -triphosphate (RTP) and triposphate (TP), have been investigated theoretically. The capability of releasing terminal phosphoric acid and existent intramolecular bonds in their structure have been studied in gas phase. Due to the presence of hydrogen bonds in the above molecules, several inner and stable rings have been formed by atoms in molecules. The Quantum Theory of Atoms in Molecules (QTAIM) has been used in order to discover the intramolecular interactions properties in terms of charge densities. We have also demonstrated that the release of terminal phosphoric acid in ATP and GTP are both facilitated in the presence of ribose and base in comparison with TP and RTP. Our calculations have been done using density functional procedure.

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Section: Resultsmentioning

confidence: 99%

Quantum chemical analysis of ATP, GTP and related compounds in gas phase

Pakiari

Farrokhnia

Moradshahi

2010

JICS

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“…Knowledge of the localization and overall shape of these orbitals will provide insight into the reactivity of the species in question. DNA, being the ''brain'' of the cell, is especially interesting to scientists who want to control the activities of the cell [61,40,66]. For this reason, attention has been paid to the frontier orbital populations of DNA [62].…”

Section: Frontier Molecular Orbital Analysismentioning

confidence: 99%

“…It has long been accepted that interactions between the highest occupied molecular orbital (HOMO) of organic molecules with the lowest unoccupied molecular orbital (LUMO) of organic molecules plays a critical role in chemical reactions of organic molecules [59,60] and larger biomolecules [61,62]. Until recently, the HOMOs and LUMOs of biomolecular systems have remained largely unstudied due to the limitations associated with quantum mechanical methods and the size of the system.…”

Section: Introductionmentioning

confidence: 99%

Quantum mechanical description of the interactions between DNA and water

Westerhoff¹,

Merz²

2006

Journal of Molecular Graphics and Modelling

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“…This rebinding can only take place when the nucleotide is in the ADP/P i product state. Some residues thought to be catalytically relevant are Glu459 (22), Ser181 (23), Ser236 (24)(25), and Gly457 (26) (using the residue numbering of Dictyostelium discoideum), which are all strictly conserved. Whereas Glu459 has been proposed to act as a general base in the catalysis, the exact role played by the other residues remained unclear.…”

mentioning

confidence: 99%

Catalytic strategy used by the myosin motor to hydrolyze ATP

Kiani

Fischer

2014

Proc. Natl. Acad. Sci. U.S.A.

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Myosin is a molecular motor responsible for biological motions such as muscle contraction and intracellular cargo transport, for which it hydrolyzes adenosine 5'-triphosphate (ATP). Early steps of the mechanism by which myosin catalyzes ATP hydrolysis have been investigated, but still missing are the structure of the final ADP·inorganic phosphate (P i ) product and the complete pathway leading to it. Here, a comprehensive description of the catalytic strategy of myosin is formulated, based on combined quantumclassical molecular mechanics calculations. A full exploration of catalytic pathways was performed and a final product structure was found that is consistent with all experiments. Molecular movies of the relevant pathways show the different reorganizations of the H-bond network that lead to the final product, whose γ-phosphate is not in the previously reported HP γ O 4 2− state, but in the H 2 P γ O 4 − state. The simulations reveal that the catalytic strategy of myosin employs a three-pronged tactic: (i) Stabilization of the γ-phosphate of ATP in a dissociated metaphosphate (P γ O 3 − ) state. (ii) Polarization of the attacking water molecule, to abstract a proton from that water. (iii) Formation of multiple proton wires in the active site, for efficient transfer of the abstracted proton to various product precursors. The specific role played in this strategy by each of the three loops enclosing ATP is identified unambiguously. It explains how the precise timing of the ATPase activation during the force generating cycle is achieved in myosin. The catalytic strategy described here for myosin is likely to be very similar in most nucleotide hydrolyzing enzymes.T he molecular motor myosin cyclically interacts with the actin filament to generate the mechanical force that is used in living cells to achieve muscle contraction (1), cytokinesis (2, 3), and intracellular cargo transport (4). Hydrolysis of one ATP molecule per cycle provides the free energy that drives the actomyosin interaction cycle, as originally described by Lymn and Taylor (5). ATP is the common energy currency in biology, and is extremely stable in aqueous solution (6, 7). ATPases, the enzymes that catalyze the hydrolysis of the P β -O-P γ anhydride linkage in ATP, are ubiquitous in biology because they are needed to accelerate the release of free energy stored in ATP. Myosin manages to speed up the hydrolysis by a factor of 10 7 over the uncatalyzed rate in solution. The experimental uncatalyzed energy barrier is 29 kcal mol −1 (7,8), and the catalyzed barrier has been determined experimentally between 14.4 kcal mol −1 (9) and 14.8 kcal mol −1 (10). Understanding how myosin achieves its ATPase function is necessary to understand how myosin works as a motor, but also helps one to understand the functioning of the multitude of other nucleotide hydrolyzing enzymes. The catalytic mechanism of ATP hydrolysis in myosin has been studied extensively with methods such as protein crystallography (11)(12)(13)(14), mutagenesis (15, 16), photochemical kinet...

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Molecular Orbital Study of the Interaction between MgATP and the Myosin Motor Domain: The Highest Occupied Molecular Orbitals Indicate the Reaction Site of ATP Hydrolysis

Cited by 17 publications

References 14 publications

Quantum chemical analysis of ATP, GTP and related compounds in gas phase

Quantum chemical analysis of ATP, GTP and related compounds in gas phase

Quantum mechanical description of the interactions between DNA and water

Catalytic strategy used by the myosin motor to hydrolyze ATP

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