Helical conformation, crystal structures

Svozil D, Kalina J, Omelka M, Schneider B (2008) DNA conformations and their sequence preferences. Nucleic acids res 36 3690-3706. doi 10.1093/nar/gkn260 Schneider B, Neidle S, Berman HM (1997) Conformations of the sugar-phosphate backbone in helical DNA crystal structures. Biopolymers 42 113-124. doi 10.1002/(SICI)1097-0282(199707)42 1<113 AID-BIP10>3.0.CO 2-0... 

Figure 13.15 Schematic diagram of the heterotrimeric Gap complex based on the crystal structure of the transducin molecule. The a suhunit is hlue with some of the a helices and (5 strands outlined. The switch regions of the catalytic domain of Gq are violet. The (5 suhunit is light red and the seven WD repeats are represented as seven orange propeller blades. The 7 subunit is yellow. The switch regions of Gq interact with the p subunit, thereby locking them into an inactive conformation that binds GDP but not GTP.

Peptoids based on a-chiral aliphatic side chains can form stable helices as well [43]. A crystal of a pentameric peptoid homooligomer composed of homochiral N-(1-cyclohexylethyl)glycine residues was grown by slow evaporation from methanol solution, and its structure determined by X-ray crystallographic methods. In the crystalline state, this pentamer adopts a helical conformation with repeating cis-... 

Molecular insight into the protein conformation states of Src kinase has been revealed in a series of x-ray crystal structures of the Src SH3-SH2-kinase domain that depict Src in its inactive conformation [7]. This form maintains a closed structure, in which the tyrosine-phosphorylated (Tyr527) C-terminal tail is bound to the SH2 domain (Fig. 2). The x-ray data also reveal binding of the SH3 domain to the SH2-kinase linker [adopts a polyproline type II (PP II) helical conformation], providing additional intramolecular interactions to stabilize the inactive conformation. Collectively, these interactions cause structural changes within the catalytic domain of the protein to compromise access of substrates to the catalytic site and its associated activity. Significantly, these x-ray structures provided the first direct evidence that the SH2 domain plays a key role in the self-regulation of Src. 

Therefore both symmetrical configurations of the hydroxy functions in the host molecule allow the helical tubuland structure. The unsymmetrical epimer anti-2,, syn-7-dihydroxy-2,7-dimethyltricyclo[4.3.1.13-8]undecane (10), the hybrid of 2 and 8, does not possess a molecular twofold axis (or pseudo twofold axis) or the conformation of C—O bonds of Fig. 5, and would not be expected to fit into the helical tubuland structure framework. Its crystal structure is indeed different, with infinite zig-zag sequences of hydrogen bonds constructing a non-including lattice 14). 

The third current approach is synthesis of peptide chains as models for the helical peptaibol (Section 8.2) and gramicidin (Section 8.3) ion channels. Considerable work has been carried out in the former area, involving synthesis of Aib-containing small peptides, in order to obtain conformational data applicable to the more complex oligopeptide antibiotics. By working with such fragments it has been possible to obtain valuable X-ray crystal structure information on the helical conformation of ala-methin 246), emerimicin 247), suzukacillin 248), and other members of the peptaibol series. 

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