PMID: 2140699Mar 20, 1990

Characterization of a vanadate-based transition-state-analogue complex of phosphoglucomutase by kinetic and equilibrium binding studies. Mechanistic implications

Biochemistry
W J Ray, J M Puvathingal

Abstract

The inhibitor complex produced by the binding of alpha-D-glucose 1-phosphate 6-vanadate to the dephospho form of muscle phosphoglucomutase exhibits an unusually small dissociation constant: about 15 fM for the Mg2+ enzyme at pH 7.4, when calculated in terms of the tetraanion. Such tight binding suggests that the enzyme/vanadate/glucose phosphate complex mimics a state that at least approaches the transition state for (PO3-) transfer in the normal enzymic reaction. This hypothesis also is supported by the observation that replacement of Mg2+, the normal metal ion activator, by Li+, a poor activator, substantially reduces the binding constant for the glucose phosphate/vanadate mixed diester. Other indicators that support this hypothesis are described. One is the derived equilibrium constant for replacement of a PO4(2-) group in bound glucose bisphosphate by VO4(2-): 3 x 10(6) when the replaced group is the phosphate at the (PO3-) transfer site of the Mg2+ enzyme--in contrast to about 10 for the same replacement (of PO4(2-) by VO4(2-)) in an aqueous solution of a phosphate ester. Another is the greatly decreased rate at which Mg2+ dissociates from the glucose phosphate/vanadate complex of the enzyme, relative to the rate at which ...Continue Reading

References

Oct 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·P P Layne, V A Najjar
Feb 10, 1978·Biochimica Et Biophysica Acta·W J RayL Ng
Jan 13, 1987·Biochemistry·J W BurgnerW J Ray
Oct 16, 1974·Journal of the American Chemical Society·R L VanEttenD M Rehkop
Jan 1, 1980·Annual Review of Biochemistry·J R Knowles

Citations

Dec 6, 1995·Molecular and Cellular Biochemistry·Debbie C CransA D Keramidas
May 30, 2001·Journal of Inorganic Biochemistry·S Bhattacharyya, A S Tracey
Feb 19, 2000·Journal of Chromatography. B, Biomedical Sciences and Applications·E M FaheyP Binding

Related Concepts

glucose-1-phosphate, sodium salt, (D-Glc)-isomer
Bos indicus
Glucosephosphates
Lithium
Magnesium
Orthophosphate
Phosphoglucomutase
Phosphorylation
Thermodynamics
Vanadyl

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