Intrinsic activity maps

Both the coupling of proton uptake to anion binding and the surprising low-temperature structural instability of the active site complex may mimic abstraction of the hydroxylic proton from a coordinated substrate molecule during turnover. Ionization of a coordinated alcohol by a base in the active site would be an important step for substrate activation in the catalytic mechanism. The nonturnover reactions serve as models for this process, giving us clearer insight into the catalytic reaction by mapping out an intrinsic proton transfer coordinate in the active site. 

While GTP-bound, die activated Ras interacts with target proteins like Raf, MEK and MAP kinase. Anodier set of proteins stimulate the intrinsic GTP hydrolytic activity of Ras and result in the termination of its activity. These proteins include GAP and neurofibromin. They recognize and interact with the effector region of p21 Ras, i.e. Raf binding sites, and may have target functions themselves. 

A EXPERIMENTAL FIGURE 14-22 Molecular structures of MAP kinase in its inactive, unphosphorylated form (a) and active, phosphorylated form (b). Phosphorylation of MAP kinase by MEK at tyrosine-185 (Y185) and threonine-183 (T183) leads to a marked conformational change in the activation lip. This change promotes dimerization of MAP kinase and binding of its substrates, ATP and certain proteins. A similar phosphorylation-dependent mechanism activates JAK kinases, the intrinsic kinase activity of RTKs, and MEK. [After B. J. Canagarajah et al., 1997,... 

Dq and ro were taken to be the free energy of activation for a parent tetrahydropyranyl alkyl acetal, and its exocyclic C-0 bond length, respectively. The plot of ln[( )/Do) -1] vs. r-rQ gives then the slope, 13.9 A and intercept 0.436. The Morse curve defined by the selected value of Dq and obtained value of / is shown in Figure 6.44. The experimental data map out a line parallel to this curve but displaced from it by 0.031 A. The authors concluded that the origin of the observed linear relationship between bond length and reactivity is to be found in the approximate linearity of the Morse function at small-to-moderate bond extensions. Since it is an intrinsic property of this function, such linear relationships may, according to Jones and Kirby, turn out to be the rule. 

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