P-hairpin

Figure 2.21 illustrates the 24 possible ways in which two adjacent p hairpin motifs, each consisting of two antiparallel p strands connected by a loop region, can be combined to make a more complex motif. 

Figure 17.11 Structure of EMPl dimer from x-ray crystallography. In the presence of EBP, the EMPl peptide forms a dimer. Each monomer (shown in red and blue) forms a p hairpin structure stabilized by hydrogen bonds (red dashes) and a disulfide bond (yellow).

The classic zinc fingers, the DNA-binding properties of which are discussed in Chapter 10, are small compact domains of about 30 residues that fold into an antiparallel p hairpin followed by an a helix. All known classic zinc fingers have a zinc atom bound to two cysteines in the hairpin and two histidines in the helix, creating a sequence motif common to all zinc finger genes. In the absence of zinc the structure is unfolded. 

Although their medium-resolution model was successful for a-helical proteins, folding P-hairpin structures have been difficult. In general, many off-lattice approaches have been tested, and although definitive proof does not exist in most cases, there appears to be a growing consensus that such off-lattice models are not sufficient. 

Pande V. S. and Rokhsar D. S. Molecular dynamics simulations of unfolding and refolding of a p hairpin fragment of protein G. (1999) (preprint). 

Blanco et al. 209 have studied the thermodynamic stability of another P-hairpin model sequence by use of NMR spectroscopy. This work was extended by Munoz et al. 201 by analysis of the T-jump-induced unfolding kinetics (with fluorescence monitoring) which revealed significantly longer time scales (ps) for bringing the two arms of the hairpin together than had previously been found for zipping the a-helix (180 ns). 

Stabilization of a P-hairpin structure can be achieved in two ways, promoting a stable (or restricted) turn structure (as done with mimetics) or linking the two arms either chemically, or, more naturally, by hydrophobic interactions. In an approach to utilizing both methods, a D-Pro-Gly linkage was used to stabilize a left-handed turn (type I or II ) and various charged and hydrophobic residues were used to stabilize the molecule and enhance the interaction between arms. I252"254 Examples of these peptides studied in nonaqueous solution by IR, VCD and NMR spectroscopy exhibit characteristics of well-formed hairpins. 255 Alternatively, in aqueous solution, IR, VCD, and ECD results for related peptides agree with the NMR interpretation of conformations characterized as hairpins stabilized at the turn and frayed at the ends. 256 These latter results also have a qualitative match with theoretical simulations. Recently, examples of hydrophobically stabilized hairpins studied by NMR spectroscopy have avoided use of a nonnatural amino acid. 257,258 ... 

Solution-state NMR studies suggest that the catalysts containing l- and D-Pro adopt p-turns and p-hairpins in solution,respectively. Reactions exhibit first-order dependence on catalyst 24, consistent with a monomeric catalyst in the ratedetermining step of the reaction. These catalysts exhibit enantiospecific rate acceleration, in comparison to the reaction rate when NMI is employed as catalyst. An isosteric replacement of an alkene for a backbone amide in a tetrapeptide catalyst (catalysts 32 and 33, Fig. 4) has lent credence to a proposed mechanism of rate acceleration [31). While catalyst 32 exhibits a fcrei=28 with substrate 27, alkene-containing catalyst 33 is not selective in this kinetic resolution and also affords a reduced reaction rate. This suggests that the prolyl amide is kinetically significant in the stereochemistry-determining step of the reaction. 

Tatko CD, Waters ML (2004) Effect of Halogenation on Edge-Face Aromatic Interactions in a P-Hairpin Peptide Enhanced Affinity with Iodo-Substituents. Org Lett 6 3969... 

Fig. 6 Triggered self-assembly of a peptide P-hairpin that forms fibrillar structures, which show facial and lateral self-assembly to hydrogel networks. Reprinted, with permission, from [96] copyright (2004) Elsevier...

It is also thought that one of the functions of UvrB is in lesion verification. A region of UvrB, a flexible p-hairpin structure, is inserted into the DNA helix to verify that the distortion represents bona fide DNA damage and to determine which strand contains the damage. Atomic force microscopy has revealed that the DNA is actually wound around the UvrB protein, and it has been suggested that the... 

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