Conformational autocatalysis

Example Conformational Autocatalysis (A Model of Prion Propagation)... 

Having such an efficient tool for predicting proteins 3D structure as the REFINER model, could we design a protein exhibiting the conformational autocatalysis ... 

Fig. 5.5 A model of conformational autocatalysis for the oligopeptide of Fig.5.4. The lowest-energy a-helical form (two-helix bundle, left-hand side) interacts with the frozen metastable (3 form (four-member (3 barrel, center). After a long Monte Carlo run (symbolized by an arrow), which consists of a million of intermediate conformations of various type, both molecules form a strong complex of two (3 type metastable forms right). During this run the a conformation unfolds and then refolds to the (3 conformation. Thus, the (3 metastable form plays a role of a catalyst in the transformation of the a native structure into the (3 form (autocatalysis)...

Example Conformational Autocatalysis as a Model of Prion Disease Propagation... 

G = glycine, V = valine, E = glutamic acid, I = isoleucine, A = alanine, K = lysine) exhibited the desired conformational autocatalysis. 

Fig. 7.14. Conformational autocatalysis, laj a two or-helix bundle conformation of a protein with a particular amino acid sequence GVEIAVKGAEVAAKVGGVEIAVKAGEVAAKVG (G = glycine, V = valine, E = glutamic acid, I = isoleucine, A = alanine, K = lysine). This 3D structure is shown in a simplified w lepiesenting a single amino acid by a point connected to its...

For example, in E. Malolepsza, M. Boniecki, A. Kolinski, L. Piela, Proc. Nat. Acad. Sciences 102 (2005) 7835 a theoretical model of the conformational autocatalysis is investigated. The native conformation of a protein becomes unstable in presence of a misfolded conformation of another molecule of the protein. The native conformation unfolds and refolds to the metastable conformation. 

Miller, B. L. Bonner, W. A. Enantioselective autocatalysis. III. Configurational and conformational studies on a 1,4-benzodiazepinooxazole derivative. Orig. Life Evol. Biosph. 1995, 25, 539-547. 

Several studies have tackled the structure of the diketopiperazine 1 in the solid state by spectroscopic and computational methods [38, 41, 42]. De Vries et al. studied the conformation of the diketopiperazine 1 by NMR in a mixture of benzene and mandelonitrile, thus mimicking reaction conditions [43]. North et al. observed that the diketopiperazine 1 catalyzes the air oxidation of benzaldehyde to benzoic acid in the presence of light [44]. In the latter study oxidation catalysis was interpreted to arise via a His-aldehyde aminol intermediate, common to both hydrocyanation and oxidation catalysis. It seems that the preferred conformation of 1 in the solid state resembles that of 1 in homogeneous solution, i.e. the phenyl substituent of Phe is folded over the diketopiperazine ring (H, Scheme 6.4). Several transition state models have been proposed. To date, it seems that the proposal by Hua et al. [45], modified by North [2a] (J, Scheme 6.4) best combines all the experimentally determined features. In this model, catalysis is effected by a diketopiperazine dimer and depends on the proton-relay properties of histidine (imidazole). R -OH represents the alcohol functionality of either a product cyanohydrin molecule or other hydroxylic components/additives. The close proximity of both R1-OH and the substrate aldehyde R2-CHO accounts for the stereochemical induction exerted by RfOH, and thus effects the asymmetric autocatalysis mentioned earlier. 

In their various permutations, the two types of models can overlap. For instance, autocatalysis (or templating) of the conformational change in PrP by PrP-res may be a feature of either the heterodimer or nucleated polymerization models (Fig. 3). However, the nucleated polymerization could also occur if PrP rapidly interchanges between high a-helix and... 

All the component reactions investigated are found to be exothermic. Initial temperature rise of bromide + bromate reaction was found to be the highest (0.55°C/min) while that of cerous + bromate + malonic acid was to be found to be quite low (0.085°C/min). Thus in the first stage, when the reaction was mixed, the latter reaction involving autocatalysis predominates and the temperature rise is very slow. On the other hand, when Br + BrOj reaction involving inhibition reaction becomes dominant, there is a sharp rise in temperature. The thermochemical behaviour is thus in conformity with the FKN mechanism (Br -control mechanism). 

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