A Classical and Ab Initio Study of the Interaction of the Myosin Triphosphate Binding Domain with ATP

Minehardt, Todd J.; Marzari, Nicola; Cooke, Roger; Pate, Edward; Kollman, Peter A.; Car, Roberto

doi:10.1016/s0006-3495(02)75429-5

Cited by 36 publications

(31 citation statements)

References 69 publications

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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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“…T he mechanism of hydrolysis of adenosine triphosphate (ATP) by myosin, leading to adenosine diphosphate (ADP) and inorganic phosphate (P i ), which constitutes one of the most important enzymatic reactions responsible for energy transduction into the directed movements of adjoining actin filaments, continues to remain a subject of active debates (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16), a significant part of which relates to what constitutes the acceptor of the proton that must be released by the ''lytic'' water in its nucleophilic attack on the ATP ␥-phosphate.…”

mentioning

confidence: 99%

Mechanism of the myosin catalyzed hydrolysis of ATP as rationalized by molecular modeling

Grigorenko

Rogov

Topol

et al. 2007

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

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The intrinsic chemical reaction of adenosine triphosphate (ATP) hydrolysis catalyzed by myosin is modeled by using a combined quantum mechanics and molecular mechanics (QM/MM) methodology that achieves a near ab initio representation of the entire model. Starting with coordinates derived from the heavy atoms of the crystal structure (Protein Data Bank ID code 1VOM) in which myosin is bound to the ATP analog ADP⅐VO 4 ؊ , a minimum-energy path is found for the transformation ATP ؉ H 2O 3 ADP ؉ Pi that is characterized by two distinct events: (i) a low activation-energy cleavage of the P ␥OO␤␥ bond and separation of the ␥-phosphate from ADP and (ii) the formation of the inorganic phosphate as a consequence of proton transfers mediated by two water molecules and assisted by the Glu-459 -Arg-238 salt bridge of the protein. The minimum-energy model of the enzyme-substrate complex features a stable hydrogen-bonding network in which the lytic water is positioned favorably for a nucleophilic attack of the ATP ␥-phosphate and for the transfer of a proton to stably bound second water. In addition, the P␥OO␤␥ bond has become significantly longer than in the unbound state of the ATP and thus is predisposed to cleavage. The modeled transformation is viewed as the part of the overall hydrolysis reaction occurring in the closed enzyme pocket after ATP is bound tightly to myosin and before conformational changes preceding release of inorganic phosphate.ATP hydrolysis ͉ enzymatic catalysis ͉ energy profile ͉ quantum mechanics and molecular mechanics simulations T he mechanism of hydrolysis of adenosine triphosphate (ATP) by myosin, leading to adenosine diphosphate (ADP) and inorganic phosphate (P i ), which constitutes one of the most important enzymatic reactions responsible for energy transduction into the directed movements of adjoining actin filaments, continues to remain a subject of active debates (1-16), a significant part of which relates to what constitutes the acceptor of the proton that must be released by the ''lytic'' water in its nucleophilic attack on the ATP ␥-phosphate.In terms of the generally accepted kinetic scheme (1-3), the relevant ATP-myosin transformations may be described by the equationin which M* and M** indicate conformers of myosin. As reported (1-3), reaction (Eq. 1) occurs with a near unit equilibrium constant K Ͻ 10 and the estimated rate constants k ϩ Ն 160 s Ϫ1 and k Ϫ Ն 18 s Ϫ1 . The rate constant k ϩ ϭ 160 s Ϫ1 can be converted to the free-energy activation barrier ⌬G # Ϸ 14.6 kcal/mol at room temperature, T ϭ 300 K, by applying a simple transition-state theory formula (17) k Ϸ 6⅐10 12 exp͓Ϫ⌬G # ͞RT͔. [2]However, noting that the experimental rate constants of reaction (Eq. 1) incorporate contributions from conformational changes in the protein from M* to M** leads us to expect that the activation energy of the intrinsic chemical reactionwhich excludes conformational rearrangements, should be considerably Ͻ14.6 kcal/mol. However, previous attempts (13, 15, 16) to simulate the mechanism of react...

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“…However, the interaction of one sub stituent group of calix [4]arene C90, which is in the M1 structure, with amino acid residues of myosin S1 probably does not refer to all sites of the enzyme related to the calix [4]arene C-90 activating the effect on ATPase. The hydrolysis of ATP is accompanied by con formational changes in the myosin S1 structural ele ments, which form its active center [20,21]. First of all, it concerns important for binding, coordination and realization of ATP hydrolysis Ploop, switch 1 and switch 2.…”

Section: +mentioning

confidence: 99%

Calix[4]arene C-90 and its analogs activate ATPase of the myometrium myosin subfragment-1

Labyntseva¹,

Bevza²,

Lytvyn³

et al. 2016

Ukr.Biochem.J.

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M yometrium contractile function is asso ciated with the activity of the main struc tural and contractile protein of uterus smooth muscle -actomyosin, in which myosin ex hibits enzyme activity, namely the ability to hydro lyze ATP. Myosin ATPase, localized in the catalytic domain of subfragment1 (S1 or head), is called a biomolecular motor. It uses the free energy of ATP hydrolysis deposited in ATP macroergic bonds for cyclic changes in the structure of the myosin head. The conformational changes in myosin active site due to ATP hydrolysis are enhanced with the assis tance of switch 1, switch 2, relay and converter and transferred to the regulatory domain -lever arm, which plays an essential role in the generation of force and movement [13]. As a result, myosin moves along the actin filament causing the muscle contrac tion. That is why myosin catalyzed ATP hydrolysis is considered as one of the most important processes in the molecular mechanism of the myometrium con traction.The known pathologies of uterus contractile function (weak labor contraction, preterm birth, miscarriage, atony, hypo and hypertonicity of the uterus, etc.) occur due to the uterine smooth mus cle contractionrelaxation dysfunction [4].Therefore, it is vital to develop new effective pharmacological substances capable of normalizing uterine func tion. The molecular basis for designing potentially bioactive compounds could be calix [4]arenes -syn thetic macrocyclic phenol oligomers, which have a cupshaped structure with various (by their chemi cal nature) substituents at the upper and lower rims. Calix[4]arenes formed by four functionalized arene fragments are characterized by rather a flexible macrocycle conformation, low toxicity of the matrix and the ability to penetrate into the cell. All these properties make calix[4]arenes promising agents for develo ping new effective drugs [5,6].Calix [4]arenes are able to modify the functional activity of certain proteins, particularly the activity of enzymes. We have previously shown that calix[4]a

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A Classical and Ab Initio Study of the Interaction of the Myosin Triphosphate Binding Domain with ATP

Cited by 36 publications

References 69 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

Mechanism of the myosin catalyzed hydrolysis of ATP as rationalized by molecular modeling

Calix[4]arene C-90 and its analogs activate ATPase of the myometrium myosin subfragment-1

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