Substrate bridge complexes

Considering the role of metals in the mechanism of enzyme-catalyzed elimination and enolization reactions, so that we might understand the role of the metal, we will restrict ourselves to those cases in which both the substrate and the enzyme donate ligands to the metal, in the ternary complex i,e, in which an enzyme-metal-substrate bridge complex (E-M-S) has been established. 

Figure 1. Distances in established enzyme-metal-substrate bridge complexes from longitudinal nuclear relaxation rates...

In ternary enzyme-metal-substrate bridge complexes, metals might activate enolization and elimination reactions by coordination of the electronegative atom (X) attached to the a carbon atom ( a activation ). 

As seen from the data in Table II, the enzyme enhances the eflFect of bound Mn on the C-3 protons of acetol phosphate, indicating the formation of an enzyme-Mn-substrate bridge complex. However, the enzyme-bound Mn has a smaller effect on the C-1 protons, indicating that the presence of the enzyme alters the structure of the Mn coordination complexes. Thus, in the absence of enzyme, from distance calculations and from stability constants, inorganic Mn forms a monodentate phosphate complex with acetol phosphate. 

Figure 5. Structures and mechanisms in aide-lase-Mn-substrate bridge complexes A. acetol phosphate, B. dihydroxyacetone phosphate Mechanism C is proposed for animal aldolases by analogy with A and B (from Ref, 22)...

Also, Chin s dihydroxy-bridged dicobalt(III) complex 10 provides one of the largest rate enhancements ever observed for phosphodiester hydrolysis [36]. Reaction with the activated phosphodiester methyl(p-nitrophenyl)phosphate (MNPP) yields 11. A crystal structure is available for the analogous dimethylphosphate complex in which the Co ions are 2.9 A apart. At pH 7 and 45 °C 11 releases p-nitrophenolate with k = 0.1 s 1 which corresponds to a nearly 10I2-fold rate enhancement over spontaneous hydrolysis of the substrate. The product of the reaction is a methylphosphate-bridged complex. Based on the pH rate profile and on... 

Chin at al. have also demonstrated [52] notable bimetallic cooperativ-ity with the same substrate by the Cu(II) complex 34. The dimer complex is 26 times more active (at pH = 7 and T = 298 K) than the corresponding mononuclear species 35. Based on the crystal structure of the dibenzyl phosphate bridged complex, the authors have proposed double Lewis-acid activation, as in the preceding case. 

Larsen, T.M., Wedeking, J.E., Rayment, I. and Reed, G.H. (1996) A carboxylate oxygen of the substrate bridges the magnesium ions at the active site of enolase structure of the yeast enzyme complexed with the equilibrium mixture of 2-phosphoglycerate and phosphoenolpyruvate at 1.8 A resolution, Biochemistry, 30, 4349-4358. 

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