Recognition sites distortion

Multiple efforts have been made to replace phosphorous-containing linkages with sulfur-containing isosteres in the context of enzyme inhibition. In a search for nonionic transition state analog inhibitors of restriction enzymes, Blattler et al. (34) found that nucleic acid duplexes that incorporate a dimethyl sulfone in place of a phosphodiester have distorted backbones similar to those in restriction enzyme bound DNA. Chimeric DNAs that incorporate sulfone hnkages were synthesized, and depending on the location of the dimethylene sulfone hnker, either between the first AT unit or the second AT unit in the EcoRV recognition site, values were 20 nM and 120... 

Figure 9.40. Distortion of the Recognition Site. The DNA is represented as a ball-and-stick model. The path of the DNA helical axis, shown in red, is substantially distorted on binding to the enzyme. For the B form of DNA, the axis is straight (not shown).

The formation of vesicular architectures from random copolymers lacking well-defined headgroups was imprecedented, proving a new method for the creation of supramolecular assemblies. This mode of assembly provides a new tool for the control of vesicle structure complementary monovalent and multivalent guests would be expected to distort or disrupt vesicle structure through competitive binding to the polymer recognition sites (31). (see Polymer Vesicles). 

Thus, the collapse of the tetrahedral adduct to the mixed anhydride intermediate is determined purely by rotation around a single C-0 bond of the tetrahedral species formed after substrate binding. The above authors have suggested that the torsional distortion of the substrate by the sites of secondary recognition provides the mechanical driving force that causes the required bond rotation to convert 50 into 51. This interpretation is supported by inspection of molecular models. 

It can therefore be concluded that the sites of secondary substrate recognition of the enzyme which impose a strain on the substrate and cause a geometrical distortion of the tetrahedral intermediate, are an obligatory part of the catalytic action of carboxypeptidase A which takes place under stere-oelectronically controlled conditions. 

Chemical modification of the biomaterial with photoisomerizable units represents one approach to controlling intermolecular affinity interactions (Scheme 2(A)). In one photoisomer state of the biomaterial, its tertiary, biologically active structure is retained and the formation of the intermolecular complex is facilitated. In the complementary photoisomer state, the bioactive binding site is distorted and the formation of the intermolecular recognition complex is switched off. The bind-... 

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