Folding isomerism

Enzymes assist formation of proper disulfide bonds during folding Isomerization of proline residues can be a rate-limiting step in protein folding Proteins can fold or unfold inside chaperonins GroEL is a cylindrical structure with a... 

In apple (Malus domestica Borkh.), flavonoid biosynthetic pathway was engineered by introducing maize leaf color (Lc) regulatory gene [73]. Leaf tissue of Lc-transgenic lines had higher levels of anthocyanin idaein (12-fold), flavan 3-ol epicatechin (14-fold), isomeric catechin (41-fold), and dimeric proanthocyanidins (7- to 134-fold). 

If the hypothesis that primary structure largely predetermines tertiary structure were correct, then folding isomerism would become irrelevant. The theory states that a given jieptide chain may be folded in two or more different ways, with each mode of folding having its own biologic property. Refolding has been... 

An example of folding isomerism might be the transition of a-keratin to j8-keratin. But the transition is forced by mechanical stretching and it is not accompanied by a change in biologic properties. The example, therefore, has no argumentative value. 

Anilines react with ct-haloacetophenones to give 2-arylindoles. In a typical procedure an W-phenacylaniline is heated with a tw o-fold excess of the aniline hydrobromide to 200-250°C[1]. The mechanism of the reaction was the subject of considerable investigation in the 1940s[2]. A crucial aspect of the reaction seems to be the formation of an imine of the acetophenone which can isomerize to an aldimine intermediate. This intermediate apparently undergoes cyclization more rapidly (path bl -> b2) than its precursor (Scheme 7.3). Only with very reactive rings, e.g, 3,5-dimethoxyaniline, has the alternative cydiz-ation (path al a2) to a 3-arylindole been observed and then only under modified reaction conditions[3],... 

Isomerization of proline residues can he a rate-limiting step in protein folding... 

In the native protein these less stable ds-proline peptides are stabilized by the tertiary structure but in the unfolded state these constraints are relaxed and there is an equilibrium between ds- and trans-isomers at each peptide bond. When the protein is refolded a substantial fraction of the molecules have one or more proline-peptide bonds in the incorrect form and the greater the number of proline residues the greater the fraction of such molecules. Cis-trans isomerization of proline peptides is intrinsically a slow process and in vitro it is frequently the rate-limiting step in folding for those molecules that have been trapped in a folding intermediate with the wrong isomer. 

In judging hindrance, it is useful to view the molecule in its three-dimensional, folded configuration. For instance, 17 can be reduced without undue difficulty, whereas 18 requires extreme conditions (Raney Ni, 2(WC, 200 atm) (7), a difference not expected from planar representations of the molecule. Saturation of A -octalin (17) may largely go through a prior isomerization to A -octa in, despite an unfavorable equilibrium 121). 

Immunophillins are abundant proteins that catalyze the cis-trans isomerization of proline residues within proteins, generally to aid in protein folding. Immunophillins are not essential proteins, are the intracellular binding proteins of several immunosuppressive drugs. Cyclosporin A exerts its action after binding to cyclophilin. Tacrolimus and sirolimus predominantly bind to the protein FKBP-12 (FK binding protein-12). 

Although a -trans- and 9-cis-RA are only minor metabolites of ROL and (3-carotene, they display 100-1000-fold higher biological activity. Whereas all-trans-RA binds only to RARs, 9-cis-RA binds both RARs and RXRs. The stereoisomer of all-irarcs-RA, 13-cis-RA, exhibits a much lower affinity for RARs and RXRs and exerts its molecular effects mostly through its isomerization into all-irarcs-RA. 

The effect of lactone ring-size on the inhibition was studied, for N-acetyl-)3-D-glucosaminidase from bovine epididymis, with lactones and lactone derivatives unable to undeigo ring-isomerization, by Pokomy and co-workers. From a comparison of Kj values for 2-acetamido-2-deoxy-D-glu-cono-1,5-lactone (0.45 nM) with the 1,4-lactone (4.5 fiM) and of Kj for the methyl ) -furanoside with that for the pyranose (4 mM), it was concluded that the 1,4-lactone has an 10-fold lower inhibitory potency than the 1,5-lactone. The weak inhibition by the 5,6-O-isopropylidene derivative of the... 

For some isomerizing species, such as LiCN/LiNC [9], quantum monodromy may be demonstrated by transporting a unit cell around a finite fold of the Em map, which joins the interleaving eigenvalues of the separate isomers. This fold therefore plays the role of the simple focus-focus singularity. 

For other isomerizing species, such as HCN/HNC [10], there is no upper m limit above which the centrifugally modified secondary well in Fig. 10 merges with the transition state. Hence the fold between the two interleaving spectra has no ends around which to transport the unit cell. Thus there is no monodromy. 

The nature of the monodromy within a given polyad was discussed. Two of the regimes allow no such monodromy one conforms to the type displayed by the swing spring, which has qualitative similarities with that in quasilinear molecules. Finally, the monodromy in the fourth regime is of the folded type, with close qualitative similarities to that observed for LiCN isomerization in Section lllB. 

Four cis isomers of P-carotene (13,15-di-di-, 15-cis-, l3-cis-, and 9-cis-) and three of a-carotene (15-di-, 13-di-, and 9-cis-) were formed during heating of their respective dll-trans carotene crystals at 50,100, and 150°C. Isomerization catalyzed by heat was considered as a reversible first-order degradation reaction — a trans-to-cis conversion two- to three-fold slower than the backward (cis-to-trans) reaction (Table 4.2.6). The 9-cis- and 13-di- were the major P-carotene isomers formed and the 13 -cis- formed at a two- to three-fold faster rate than O-cw-P-carotene. In this system, a-carotene showed lower stability than P-carotene (Table 4.2.6). The activation energy (EJ was not reported since practically no degradation was observed... 

The presence of a hot spot is known to generate free radicals. Thus, reactions that are initiated by the presence of free radicals can be carried out with less or no catalyst, as has been discovered in the case of isomerization of maleic acid to fumaric acid with an 3 to 16 fold increase in the isomerization rates at reduced catalyst (thiourea) concentrations (Muzumdar, 1988). 

Muller et al. focused on polybead molecules in the united atom approximation as a test system these are chains formed by spherical methylene beads connected by rigid bonds of length 1.53 A. The angle between successive bonds of a chain is also fixed at 112°. The torsion angles around the chain backbone are restricted to three rotational isomeric states, the trans (t) and gauche states (g+ and g ). The three-fold torsional potential energy function introduced [142] in a study of butane was used to calculate the RIS correlation matrix. Second order interactions , reflected in the so-called pentane effect, which almost excludes the consecutive combination of g+g- states (and vice-versa) are taken into account. In analogy to the polyethylene molecule, a standard RIS-model [143] was used to account for the pentane effect. 

The 14-membered macrocycle 1,4,8,11-tetraazacyclotetradecane (cyclam or [14]aneN4), unlike cyclen, is capable of encircling most transition metal ions and in the case of Co111 the trans configuration is much preferred by comparison with the folded cis isomer. Electrochemical reduction of A,v-[Co(cyclam)(OI I)2]+ in 3M NaOH leads to rapid isomerization to the trans form, and the relative stabilities of the trans and cis isomers of the di- and trivalent complexes were determined from a thermodynamic cycle.702 This preference for trans orientation of the non-macrocyclic donors has enabled the isolation and investigation of many Co complexes without the complications of isomerization. Some novel examples include /r[Pg.61]

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