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Link to original content: https://pubmed.ncbi.nlm.nih.gov/12721374/
The rate of hydrolysis of phosphomonoester dianions and the exceptional catalytic proficiencies of protein and inositol phosphatases - PubMed Skip to main page content
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. 2003 May 13;100(10):5607-10.
doi: 10.1073/pnas.0631607100. Epub 2003 Apr 29.

The rate of hydrolysis of phosphomonoester dianions and the exceptional catalytic proficiencies of protein and inositol phosphatases

Chetan Lad  1 , Nicholas H Williams, Richard Wolfenden
Affiliations

The rate of hydrolysis of phosphomonoester dianions and the exceptional catalytic proficiencies of protein and inositol phosphatases

Chetan Lad et al. Proc Natl Acad Sci U S A. .

Abstract

To evaluate the proficiency of phosphatases as catalysts, the rate of the uncatalyzed hydrolysis of simple phosphate monoester dianions was estimated by extrapolating rates measured over a range of high temperatures. The rate of spontaneous hydrolysis of phenyl phosphate dianion indicates that a linear free energy relationship reported earlier is reliable for leaving groups whose conjugate acids have pKa values up to at least 10. Using Teflon reaction vessels, it proved possible to follow the hydrolysis of methyl phosphate and 3-(4-carboxy)-2,2-dimethylpropyl phosphate in strong alkali. Even in 1 M KOH, the reaction was found to be specific acid catalyzed. These results establish an upper limit for dianion reactivity, which had been overestimated earlier as a result of the leaching by alkali of silicic acid from quartz reaction vessels. The present findings indicate that the half-time for attack by water on alkyl phosphate dianions is 1.1 x 10(12) years (k = 2 x 10(-20) s) at 25 degrees C and that phosphatases involved in cell signaling and regulation produce the largest rate enhancements that have been identified thus far. Protein phosphatase-1 and inositol 1-phosphatase exceed all other known enzymes in their affinities for the altered substrates in the transition state.

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Figures

Figure 1
Figure 1
Linear free energy relationship between leaving-group pKa values and rate constants for hydrolysis of phosphate monoester dianions at 39°C. ○, benzoyl (9) and aryl (12) phosphates. ●, phenyl phosphate (present work). □, MeP (7). ■, present data. The line shown is corresponds to that in ref. and is described by the equation 0.862 − 1.23 pKa.
Scheme 1
Scheme 1
Compound 1.
Figure 2
Figure 2
Observed first-order rate constants for hydrolysis in 1 M KOH of phenyl phosphate (○), compound 1 (□), and MeP2− (▵), plotted as a function of reciprocal temperature (Kelvin).
Figure 3
Figure 3
Half-times of biological reactions proceeding spontaneously in water at 25°C in the absence of a catalyst (for earlier references, see ref. 1).
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