Helicity reactions

Figure C3.2.6. Zones associated witlr the distinctive decay of electronic coupling tlrrough a-helical against p-sheet stmctures in proteins. Points shown refer to specific rates in mtlrenium-modified proteins aird in tire photosyntlretic reaction centre. From Gray H B aird Wiirkler J R 1996 Electron trairsfer in proteins A . Rev. Biochem. 65 537.

In biological systems molecular assemblies connected by non-covalent interactions are as common as biopolymers. Examples arc protein and DNA helices, enzyme-substrate and multienzyme complexes, bilayer lipid membranes (BLMs), and aggregates of biopolymers forming various aqueous gels, e.g, the eye lens. About 50% of the organic substances in humans are accounted for by the membrane structures of cells, which constitute the medium for the vast majority of biochemical reactions. Evidently organic synthesis should also develop tools to mimic the Structure and propertiesof biopolymer, biomembrane, and gel structures in aqueous media. 

Figure 4.7 Two of the enzymatic activities involved in the biosynthesis of tryptophan in E. coli, phosphoribosyl anthranilate (PRA) isomerase and indoleglycerol phosphate (IGP) synthase, are performed by two separate domains in the polypeptide chain of a bifunctional enzyme. Both these domains are a/p-barrel structures, oriented such that their active sites are on opposite sides of the molecule. The two catalytic reactions are therefore independent of each other. The diagram shows the IGP-synthase domain (residues 48-254) with dark colors and the PRA-isomerase domain with light colors. The a helices are sequentially labeled a-h in both barrel domains. Residue 255 (arrow) is the first residue of the second domain. (Adapted from J.P. Priestle et al., Proc.

Figure 4.14 Examples of different types of open twisted a/p structures. Both schematic and topological diagrams are given. In the topological diagrams, arrows denote strands of p sheet and rectangles denote a helices, (a) The FMN-binding redox protein flavodoxln. (b) The enzyme adenylate kinase, which catalyzes the reaction AMP +...

Figure 12.14 The three-dimensional structure of a photosynthetic reaction center of a purple bacterium was the first high-resolution structure to be obtained from a membrane-bound protein. The molecule contains four subunits L, M, H, and a cytochrome. Subunits L and M bind the photosynthetic pigments, and the cytochrome binds four heme groups. The L (yellow) and the M (red) subunits each have five transmembrane a helices A-E. The H subunit (green) has one such transmembrane helix, AH, and the cytochrome (blue) has none. Approximate membrane boundaries are shown. The photosynthetic pigments and the heme groups appear in black. (Adapted from L. Stryer, Biochemistry, 3rd ed. New York ...

Figure 12.16 View of the reaction center perpendicular to the membrane illustrating that the pigments are bound between the transmembrane helices. The five transmembrane-spanning a helices of the L (yellow) and the M (red) subunits are shown as well as the chlorophyll (green) and pheophytin (blue) molecules.

In contrast to bacteriorhodopsin or the reaction center, there is no direct contact within the membrane between the a helices in this complex. The helices are held together through contacts mediated by the pigments and by contacts at the ends of the polypeptide chains outside the membrane. 

In contrast, the transmembrane helices observed in the reaction center are embedded in a hydrophobic surrounding and are built up from continuous regions of predominantly hydrophobic amino acids. To span the lipid bilayer, a minimum of about 20 amino acids are required. In the photosynthetic reaction center these a helices each comprise about 25 to 30 residues, some of which extend outside the hydrophobic part of the membrane. From the amino acid sequences of the polypeptide chains, the regions that comprise the transmembrane helices can be predicted with reasonable confidence. 

When the hydropathy indices are plotted against residue numbers, the resulting curves, called hydropathy plots, identify possible transmemhrane helices as broad peaks with high positive values. Such hydropathy plots are shown in Figure 12.23 for the L and M chains of the reaction center. 

Figure 12.23 Hydropathy plots for the polypeptide chains L and M of the reaction center of Rhodobacter sphaeroides. A window of 19 amino acids was used with the hydrophohicity scales of Kyte and Doolittle. The hydropathy index is plotted against the tenth amino acid of the window. The positions of the transmembrane helices as found by subsequent x-ray analysis by the group of G. Feher, La Jolla, California, ate indicated by the green regions.

The hydropathy plots in Figure 12.23 were calculated and published several years before the x-ray structure of the reaction center was known. It is therefore of considerable interest to compare the predicted positions of the transmembrane-spanning helices with those actually observed in the x-ray structure. These observed positions are indicated in green in Figure 12.23. 

Comparison of the amino acid sequences of the L and M subunits of the reaction centers from three different bacterial species shows that about 50% of all residues in those two subunits are conserved in all three species. In the transmembrane helices, sequence conservation varies. Residues that are buried and have contacts either with pigments or with other transmembrane helices are about 60% conserved. In contrast, residues that are fully exposed to the membrane lipids are only 16% conserved. Clearly, fewer restrictions... 

Table 12.2 Amino acid sequences of the transmembrane helices of the photosynthetic reaction center in Rhodobacter sphaeroides...

The most important general lesson is that there are hydrophobic transmembrane helices, the positions of which within the amino acid sequence can be predicted with reasonable accuracy. This applies both to the single transmembrane-spanning helix within the H polypeptide chain of the reaction center and the five transmembrane helices of the L and M chains that... 

The structure of the reaction center also established that membrane-spanning helices can be tilted with respect to the plane of the membrane and that their relative positions within the membrane might be determined by the way they are anchored to the loop regions. Finally, several structures provide examples of how binding pockets for ligands are formed between such transmembrane-spanning helices. 

Like the photosynthetic reaction center and bacteriorhodopsin, the bacterial ion channel also has tilted transmembrane helices, two in each of the subunits of the homotetrameric molecule that has fourfold symmetry. These transmembrane helices line the central and inner parts of the channel but do not contribute to the remarkable 10,000-fold selectivity for K+ ions over Na+ ions. This crucial property of the channel is achieved through the narrow selectivity filter that is formed by loop regions from thefour subunits and lined by main-chain carbonyl oxygen atoms, to which dehydrated K ions bind. 

The ion pore has a narrow ion selectivity filter The bacterial photosynthetic reaction center is built up from four different polypeptide chains and many pigments The L, M, and H subunits have transmembrane a helices... 

Cyclopentadiene, b.p. 40°, is obtained by heating commercial 85% dicyclopentadiene (e.g., from Matheson, Coleman and Bell Company, Norwood, Ohio) under a short column (M in. diameter X 8-12 in. length) filled with glass helices. The distilled cyclopentadiene is collected in a receiver which is maintained at Dry Ice temperature until the cyclopentadiene is used. Methylcyclopentadiene and other substituted cyclopentadienes such as indene may also be employed for the synthesis of the correspondingly substituted ferrocenes. In these cases, the reaction of the hydrocarbon with sodium is much slower than with cyclopentadiene, and refluxing for several hours is required to complete the reaction. 

The compounds are isolated by sublimation from the reaction mixture. Perhaps surprisingly the compounds fall into two quite distinct classes. Those of Np and Pu are unstable, volatile, monomeric liquids which at low temperatures crystallize with the 12-coordinate structure of Zr(BFl4)4 (Fig. 21.7, p. 969). The borohydrides of Th, Pa and U, on the other hand, are thermally more stable and less reactive solids. They possess a curious helical polymeric structure in which each An is surrounded by 6 BFI4 ions, 4 being bridging groups attached by 2 FI atoms and... 

Yamamoto et al. have reported a chiral helical titanium catalyst, 10, prepared from a binaphthol-derived chiral tetraol and titanium tetraisopropoxide with azeotropic removal of 2-propanol [16] (Scheme 1.22, 1.23, Table 1.9). This is one of the few catalysts which promote the Diels-Alder reaction of a-unsubstituted aldehydes such as acrolein with high enantioselectivity. Acrolein reacts not only with cyclo-pentadiene but also 1,3-cyclohexadiene and l-methoxy-l,3-cyclohexadiene to afford cycloadducts in 96, 81, and 98% ee, respectively. Another noteworthy feature of the titanium catalyst 10 is that the enantioselectivity is not greatly influenced by reaction temperature (96% ee at... 

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