Conformational change, fructose

A central event in the allosteric mechanism is the rotation of the dimers relative to each other. The movement is coupled with the conformational change of all four binding sites for fructose-6-P, since this is foimd at the dimer interace. 

Methylation is still conducted in much the same manner as previously, except that the use of such solvents as A, A-dimethylformamide and methyl sulfoxide is widely accepted it results in higher yields and in conformational changes. - For example, the furanose ethers are formed when A,iV -dimethyhormamide is used as the solvent during the methylation of D-fructose, and most of the reducing monosaccharides are now methylated at room temperature in one step. Many of these ethers have already been described in this Series, fundamental structure-analysis being based on the identification of the different methyl derivatives, but the ones that were then missing and which have since been synthesized are discussed below. 

Phosphofructokinase was one of the first enzymes to which Monod and his colleagues applied the symmetry model of allosteric transitions. It contains four identical subunits, each of which has both an active site and an allosteric site. The cooperativity of the kinetics suggests that the enzyme can adopt two different conformations (T and R) that have similar affinities for ATP but differ in their affinity for fructose-6-phosphate. The binding for fructose-6-phosphate is calculated to be about 2,000 times tighter in the R conformation than in T. When fructose-6-phosphate binds to any one of the subunits, it appears to cause all four subunits to flip from the T conformation to the R conformation, just as the symmetry model specifies. The allosteric effectors ADP, GDP, and phosphoenolpyruvate do not alter the maximum rate of the reaction but change the dependence of the rate on the fructose-6-phosphate concentration in a manner suggesting that they change the equilibrium constant (L) between the T and R conformations. 

Phosphatases specific for such substrates as glucose-6-phosphate, fructose-l,6-bisphosphate, and phospho-glycolate help to drive metabolic cycles (Chapter 17). The 335-residue fructose-1,6-bisphosphatase associates to form a tetramer with D2 symmetry. ° The allosteric enzyme exists in two conformational states (see Chapter 11). Activity is dependent upon Mg + or other suitable divalent cation, e.g., Mn or Zn, and is further enhanced by K+ or NH3. While the dimetal sites depicted in Figs. 12-23 and 12-24 are quite rigid and undergo little change upon formation of complexes with substrates or products, the active site of fructose-1,6-bisphosphatase is more flexible. There are three metal-binding sites but they contain no histidine side chains and have been seen clearly only in a product complex. Perhaps because of the need for... 

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