Binding, directional preferences

Mg2+ binds directly to the phosphate oxygen atoms and through a water molecule to the carboxylate group. Since Mg2+ prefers an octahedral coordination sphere, it requires a water structure different from that observed in holo rhamnulose kinase. 

A puzzling discovery was that the motor domain of kinesin, which binds primarily to the P subunits of tubulin (Fig. 7-34) and moves toward the fast growing plus end of the microtubule, is located at the N terminus of the kinesin molecule, just as is myosin. However, the Ned and Kar3 motor domains are at the C-terminal ends of their peptide chains and move their "cargos" toward the minus ends of microtubules. Nevertheless, the structures of all the kinesin heads are conserved as are the basic chemical mechanisms. The differences in directional preference are determined by a short length of peptide chain between the motor domain and the neck, which allows quite different geometric arrangements when bound to microtubules. Like Ned, myosin VI motor domains also move "backwards" toward the pointed (minus) ends of actin filaments. " ... 

Analyses of packing in crystals have, in many cases, shown that there are directional preferences of binding. The nature of this directionality appears to depend on the partial charges developed on the interacting atoms. Some examples will now be described. 

Surroundings of covalently bound sulfur atoms in crystal structures provide an excellent example of the directionality of intermolecular interactions. Directional preferences of binding around divalent sulfur bonded to two other atoms (XSY where X and Y are commonly carbon) were studied in a wide variety of crystal structures. This was one of the early analyses of intermolecular interactions in crystal structures, before the CSD was generally available [18]. The analysis was made on nonbonded contacts, up to 4.2 A from the sulfur atoms it showed, as indicated in Fig. 5, that the locations of functional groups around the CSC group depend on their (partial) charges. 

Fig. 5a-c Directional preferences of binding of X-S-Y groups a diagram of the directions in which charged groups approach the sulfur atom b chemical formula of mesolanthionine dihydrochloride... 

Fig. 6a-c. Directional preferences of binding of disulfide (-S-S- groups) a diagram of the interactions (Xj, X2, Y, Yj = any atom) b chemical formula of 4,5-bis(methylsulfanyl)-l,2-dithiole-3-thione c stereoview of the S "S interactions in 4,5-bis(methylsulfanyl)-l,2-dithiole-3-thione [112]... 

We are now learning much about intermolecular interactions and reactions from the types of studies described here. An understanding of directional preferences of binding of functional groups is an essential starting point for proposals on mechanisms of reactions between two molecules, large or small, and also for the construction of supramolecular assembHes,be they in solution or in the soUd state, the latter being in the focus of interest here. 

---