23583-49-5Relevant articles and documents
'Active' conformation of the inositol monophosphatase substrate, adenosine 2'-phosphate: role of the ribofuranosyl O-atoms in chelating a second Mg2+ ion
Cole, Andrew G.,Gani, David
, p. 2685 - 2694 (2007/10/02)
In the presence of Mg2+ ions, inositol monophosphatase from bovine brain catalyses the hydrolysis of the phosphate ester of a range of purine- and pyrimidine-containing nucleoside 2'-phosphates including adenosine 2'-phosphate (2'-AMP) but not adenosine 2'-phosphorothioate (2'-AMPS). 2'-AMPS also fails to serve as an inhibitor under these conditions.In contrast to the situation for the alcohol hydrolysis product, inositol, adenosine does not serve as a product inhibitor for the enzyme or mediate the enzyme-catalysed exchange of 18O-label from water into inorganic phosphate.However, in the presence of Mn2+ ions 2'-AMPS is a substrate for the enzyme.These findings indicate that the product adenosine does not bind to the enzyme in its ground-state conformations and that a strong phosphate group-holoenzyme interaction is required to stabilise a high-energy arrangement in the enzyme-substrate complexes of 2'-AMPS and, probably, 2'-AMP.On the basis of these results and those from previous kinetic and substrate modification studies it is proposed that a second Mg2+ ion might stabilise a conformation in which the adenine moiety of bound 2'-AMP occupies a C-1'-axial ribofuranosyl position through the direct chelation of the second Mg2+ ion to the bridging phosphate ester 2'-O-atom and the ribofuranose ring O-atom.An alternative high-energy arrangement in which the interaction of the second Mg2+ ion with the ribofuranose ring O-atom is mediated via water, such that the conformational strain in the furanose ring is relaxed, but where the entropy of the water is decreased, is also a possibility.
