Abstract
The structural analogy with phosphate derives arsenate into various metabolic processes associated with phosphate inside the organisms. But it is difficult to evaluate the effect of arsenate substitution on the stability of individual biological phosphate species, which span from a simpler monoester form like pyrophosphate to a more complex phosphodiester variant like DNA. In this study, we have classified the physiological phosphate esters into three different classes on the basis of their structural differences. This classification has helped us to present a concise theoretical study on the kinetic stability of phosphate analogue species of arsenate against hydrolysis. All the calculations have been carried out using QM/MM methods of our Own N-layer Integrated molecular Orbital molecular Mechanics (ONIOM). For quantum mechanical region, we have used M06-2X density functional with 6-31+G(2d,2p) basis set and for molecular mechanics we have used the AMBER force field. The calculated rate constants for hydrolysis show that none of the phosphate analogue species of arsenate has a reasonable stability against hydrolysis.
Highlights
Maintaining negative charge at physiological pH leads phosphate (PO24À or Pi) ester to dominate the living world as it prevents chemically stored energy and genetic material from escaping the cell [1]. (V) is capable of retaining negative charge in its phosphate analogue arsenate (AsO24À or Asi) over a range of physiological pH conditions [2] and it is already demonstrated in bacteria that at a high concentration ratio of Asi/Pi the phosphate transporters allow the transport of Asi on the basis of structural similarity [3]
Our study aims at comparing the kinetic stability of As and P esters against water, we only modelled the reactants and transition state (TS) structures which belong to the rate determining step
We found that there is no significant difference among the rate constants of monoanionic pyro-Asi and ribose-1-Asi, monoionic pyro-Pi and ribose-1-Pi, similar to the dianionic species of both the esters, which signifies that the conserved sites through which these two esters bonded covalently have nothing to do with the kinetics of the hydrolysis
Summary
Maintaining negative charge at physiological pH leads phosphate (PO24À or Pi) ester to dominate the living world as it prevents chemically stored energy and genetic material from escaping the cell [1]. (V) is capable of retaining negative charge in its phosphate analogue arsenate (AsO24À or Asi) over a range of physiological pH conditions [2] and it is already demonstrated in bacteria that at a high concentration ratio of Asi/Pi the phosphate transporters allow the transport of Asi on the basis of structural similarity [3]. (V) is capable of retaining negative charge in its phosphate analogue arsenate (AsO24À or Asi) over a range of physiological pH conditions [2] and it is already demonstrated in bacteria that at a high concentration ratio of Asi/Pi the phosphate transporters allow the transport of Asi on the basis of structural similarity [3]. This structural analogy further leads to the integration of Asi into various metabolic processes associated with Pi inside the organisms [2], whereas the primary. Through a unique classification of Pi biomolecules, we examined the consequence of Asi substitution on the kinetic stability of Pi species spanning from a simpler monoester form like pyrophosphate to a more complex phosphodiester variant like DNA
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