Pseudorotation mechanism of ATP hydrolysis in muscle contraction

Young, John H.; McLick, Jerome; Korman, Ephraim F.

doi:10.1038/249474a0

Cited by 27 publications

(16 citation statements)

References 22 publications

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“…The current evidence (Bagshaw et al, 1975) is consistent with the relevant step being that of the hydrolytic cleavage of ATP (eq 3) and the problem will be treated on this basis. The derivation is equally applicable to other possible mechanisms, involving pentacoordinate intermediates (Young et al, 1974), metaphosphate (Sartorelli et al, 1966), or phosphorylated protein intermediates. This general problem has been examined by Boyer et al (1977) but the outline is given here explicitly for the case of intermediate exchange.…”

Section: Methodsmentioning

confidence: 99%

Effect of actin concentration on the intermediate oxygen exchange of myosin; relation to the refractory state and the mechanism of exchange

Sleep¹,

Boyer²

1978

Biochemistry

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The effect of actin concentration on the myosin catalyzed exchange of phosphate oxygens with water accompanying ATP hydrolysis has been investigated. The extent of exchange was found to extrapolate to zero at infinite actin concentration at 23 and 0 degrees C for myosin subfragments S1(A1) and S1(A2). This result is consistent with actin associating directly with the product of the hydrolysis step and is not readily consistent with refractory state schemes in which the entire flow goes via a dissociating pathway. The possibility of a refractory state in the form of a phosphorylated intermediate or a bound metaphosphate state with hydrolysis occurring in the transition to the refractory state merits consideration. A full analysis of the dependence of intermediate exchange on the rate constants of the acto-S1 scheme is given and the errors arising from other methods of analysis are discussed. The rate of oxygen exchange was measured as 10 s-1 (23 degrees C) a value comparable with but slightly lower than the rate of reversal of the ATP cleavage step.

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Section: Methodsmentioning

confidence: 99%

Effect of actin concentration on the intermediate oxygen exchange of myosin; relation to the refractory state and the mechanism of exchange

Sleep¹,

Boyer²

1978

Biochemistry

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“…It has been proposed that ATP hydrolysis catalysed by ATPases involves a pseudo-rotation mechanism (Korman & McLick, 1973). In the case of myosin, Young, McLick & Korman (1974) consider that the M*.ATP to M** .ADP .Pi transformation represents a pseudo-rotation of ATP (i.e. ATP is not cleaved).…”

Section: O Analysismentioning

confidence: 99%

Kinetic Analysis of ATPase Mechanisms

Trentham¹,

Eccleston²,

Bagshaw³

1976

Quart. Rev. Biophys.

286

180

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At even the simplest level we can expect an ATPase mechanism to comprise the following four steps: the binding of ATP, the reaction of ATP with water on the enzyme, and the release of the products ADP and P1. So at the outset techniques are needed to investigate these four processes. The range of techniques needed is soon extended once questions are asked about the role of protons and metal ions, the possibility of a multistep hydrolytic process, multistep substrate and product binding processes, and protein–lipid or protein–protein interactions. Since ATPases and ATP synthases are almost universally involved in some form of energy transduction there is a particular need in an ATPase or ATP synthase reaction to evaluate the equilibrium constants of the steps in the mechanism and to investigate the possibility of alternate reaction pathways. The nature of the coupling process by the protein of the chemical reactions of ATP to the other energetic process, be it muscle contraction, active transport, respiration or photosynthesis, is likewise of profound interest. Finally we would like to know as much as possible about the ATPase or ATP synthase mechanism during the period when the various forms of energy transduction are occurring.

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“…In simplest terms it is the step in which the covalent terminal phosphate bond of the bound ATP is broken. However, on the basis of current knowledge, it could also represent the transformation of a pentavalent phosphate intermediate to a more labile form which subsequently cleaves (Young et al, 1974). The ratelimiting step in the sequence is step 4 which for myosin acting alone is exceedingly slow .…”

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confidence: 99%

Mechanism of oxygen exchange in actin-activated hydrolysis of adenosine triphosphate by myosin subfragment 1

Shukla¹,

Levy²

1977

Biochemistry

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The gamma-phosphoryl groups of two intermediates (M-ATP and M-ADP-P1) in the pathway of MgATP hydrolysis by myosin undergo extensive oxygen exchange with water. Actin activates the overall rate of hydrolysis at a rate-limiting step which follows these exchange reactions. Thus, actin, by decreasing the turnover time of hydrolysis, would be expected to proportionately decrease the time available for oxygen exchange. Using subfragment 1 of myosin, the turnover time of hydrolysis can be varied over a wide range by changing the concentration of actin. An estimate for the rate constant of exchange can then be obtained by relating these turnover times to measured values for oxygen exchange (incorporation of 18O from H218O into the inorganic phosphate (Pi) released by hydrolysis). The results of such an experiment, with turnover times between 0.2 and 25 s, indicate that, for each gamma-phosphoryl group, one oxygen from the medium is added rapidly (to cleave the phosphoryl group or form a pentacoordinate phosphroyl complex); two more oxygens exchange with a rate constant, kc, of about 1 s-1; and a fourth oxygen exchanges slowly with ke about 0.2 s-1. The higher value is about 18 times smaller than the rate constant, 5-3, for the reverse cleavage step of the myosin pathway, which is postulated to be responsible for oxygen exchange. The data, then, indicate that the rate-limiting step for oxygen exchange is not k-3, but may be the rate of rotation of oxygens around the phosphorus atom, with one oxygen severely restricted by its binding to the active site. The finding that kc differs for the four oxygens in each phosphate group is related to past observations on myosin-catalyzed oxygen exchange.

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Pseudorotation mechanism of ATP hydrolysis in muscle contraction

Cited by 27 publications

References 22 publications

Effect of actin concentration on the intermediate oxygen exchange of myosin; relation to the refractory state and the mechanism of exchange

Effect of actin concentration on the intermediate oxygen exchange of myosin; relation to the refractory state and the mechanism of exchange

Kinetic Analysis of ATPase Mechanisms

Mechanism of oxygen exchange in actin-activated hydrolysis of adenosine triphosphate by myosin subfragment 1

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