Binding sites, spatial relationships

An alternative approach is that adopted by Horrocks and co-workers, where the aromatic residues in metal-binding proteins are used as sensitizers. Since the distance between the metal and the donor is effectively fixed, this provides a rigid scaffold for the experiment, and the absence of a directly conjugated pathway between the metals means that Forster (through space) energy transfer can be assumed. The r-6 distance-dependence of this means that the extent of sensitized emission from the lanthanide ion provides information on the spatial relationship between the metal-ion binding site (lanthanide ions often bind at Ca2+ sites) and nearby aromatic residues. 58-60... 

Iodoacetyl-LC-biotin has been used to localize the SH thiol of myosin by use of an avidin-biotin complex visualized by electron microscopy (Sutoh et al., 1984) and to determine the spatial relationship between SHj and the actin binding site on the myosin subfragment-1 surface (Yamamoto et al., 1984). 

Yamamoto, K., Sekine, T., and Sutoh, K. (1984) Spatial relationship between SHI and the actin binding site on myosin subfragment-1 surface. FEES Lett. 176, 75-78. 

Spatial Relationships of the Anion and Metal Binding Sites... 

From a stereochemical analysis of binding anions, the interlocking-sites model is most consistent with available data. We have approached the question of the spatial relationship of metal ion and anion in human transferrin through electron and nuclear magnetic resonance spectroscopy (17,49). 

Fig. 8. Spatial relationship between the three copper sites in a multicopper oxidase. The structure (and residue numbering) is a representation of these sites in hCp. The trinuclear cluster is a near-isosceles triangle, 3.4 A on a side. The notation Cu(2) and Cu(3) is taken from Messerschmidt et al. (1992a) and corresponds to the notation Type 3" and Type 3, respectively, used by Zaitseva et al. (1996). Oxygen is thought to bind between the type 2 copper and Cu(2).

Figure 5.6. Spatial relationship of the binding sites for diethy-lamine and aniline, respectively, on the Nay channel. Left If the binding sites were distantly located, lidocaine should only be able to interact with one site at a hme. Right The substantially higher affinity observed with lidocaine as compared to its components suggests that the two sites are close to each other.

Gupta et al. [72] performed an extensive structure-activity comparison regarding cross-resistance in two emetine-resistant CHO cell variants. This study showed that phenanthroindolizidine alkaloids, phenanthroquinolizidine alkaloids, and emetine-related benzoquinolizidines may have the same site of action. The conformation of emetine was suggested to have a close spatial relationship to the other three compound classes, and thus, they could bind to the same hypothetical binding site, Fig. (7). 

In inactive kinase structures, two or more of the above mentioned structural elements are aligned in a way that prevents substrate binding and/or catalysis. Fig 7.4 shows the spatial relationship of the critical protein kinase activity modulation sites. 

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