Finding Binding Pockets

To probe whether the binding pocket exerts an effect on the stability of the complexes, a series of diamagnetic zinc complexes [Zn2(L19)(02CR)] + 49a-f bearing different carboxylate coligands was prepared and analyzed by NMR spectroscopy in the solution state (Table III). The most important findings of these investigations are as follows ... 

These conclusions are still consistent with the finding that significant conformational differences between Pr and Pfr do in fact exist ([65,147] for reviews see [8c, 148]). They can be rationalized—albeit not with conclusive rigour—by a conformational adaptation of the apoprotein part located around the bilatriene-binding pocket, following the Z E photoisomerization of the chromophore. This local change then should suffice to determine through bilatriene chromophore-protein interactions the spectroscopic characteristics of the chromophore as well as stability and reactivity of the two photochromic forms of phytochrome. 

Figure 13.2 features the currently practiced paradigm of structure-based drug design (Dixon, 1992). The key step, besides finding an inhibitory compound, is the elucidation of the 3D structure of the complex between the binding pocket and inhibitor. 

These assumptions are further supported by the finding that mutations that are believed to alter the geometry of the binding pocket or the conformational changes... 

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