Structure P-hairpin

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).

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. 

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 ... 

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... 

As expected, mutation of the active site Asp30 to Asn did not affeet the overall stmcture of the protein. FIV PR(D30N) is a homodimer (117 residues per monomer, including N-terminal alanine). The tertiary structure of the monomer consists mainly of P sheets and turns and is similar to that of FIV PR(wt) (12). The two monomers are related hy a two-fold axis. The active site, characterized by AsnA30, AsnB30 and the inhibitor molecule LP-149 (Fig. 1), is located between the two monomers (To simplify the description of the dimer, letters A and B are arbitrarily used to describe the residues contributed by the two different monomers for residues adopting two different conformations, we denoted their second conformation by primes). The flaps, two P hairpin structures formed by residues A49-A69 and B49-B69, fold over the inhibitor in the active site. Their position and conformation are similar to those observed in the wild type structure (12). Residues A59-A61 (and B59-B61), which form the tip of the flaps adopt two conformations,... 

Hur and Bruice carried out classical molecular dynamics on the complex of ODCase with OMP before decarboxylation, as well as the putative intermediate (the C6 anion) formed by decarboxylation [39]. Based on these calculations, it was proposed that loop movement in ODCase may play a key role in catalysis a stable p hairpin structure appeared to form during decarboxylation that was not present before decarboxylation. In addition, the structure of OMP in aqueous solution was also simulated, and the similarity of the conformations of OMP in water and in the ODCase active site suggested that OMP is not bound in a particularly strained fashion, further arguing against a Circe effect. 

Framework model The protein folding begins with the secondary structures. This is followed by docking of the pre-formed secondary structure units to produce the native, folded macromolecule (Kim and Baldwin, 1990). For small proteins with stable secondary structure(s), they tend to adopt a-helical and turn or P-hairpin structures. These structures may start the folding process. 

E. de Alba, M. A. Jimenez, M. Rico, and J. L. Nieto, Conformational investigation of designed short linear peptides able to fold into p-hairpin structures in aqueous solution. Fold. Des. 1(2), 133-144 (1996). 

S. Honda, N. Kobayashi, and E. Munekata, Theormodynamics of a P-hairpin structure Evidence for cooperative formation of folding nucleus. J. Mol. Biol. 295(2), 269-278 (2000). 

The stereoselectivity was improved through the preparation of p>entapeptide 19, in which the oxygen of the amide between proline and the Aib residue was replaced by a sulfur atom, with the thioamide considered as an isostere of the amide. The NH of a thioamide can form a stronger hydrogen bond than an amide NH considering its more acidic character [32]. A further improvement was reported with the insertion of a sulfonamide in fact the tosyl group on the a-amino of the histidine residue enhances the stability of the second interstrand hydrogen bond in the P-hairpin structure [33]. 

The simplest topology is obtained if each successive p strand is added adjacent to the previous strand until the last strand is joined by hydrogen bonds to the first strand and the barrel is closed (Figure 5.2). These are called up-and-down P sheets or barrels. The arrangement of p strands is similar to that in the a/P-barrel structures we have just described in Chapter 4, except that here the strands are antiparallel and all the connections are hairpins. The structural and functional versatility of even this simple arrangement will be illustrated by two examples. 

We saw in Chapter 2 that the Greek key motif provides a simple way to connect antiparallel p strands that are on opposite sides of a barrel structure. We will now look at how this motif is incorporated into some of the simple antiparallel P-barrel structures and show that an antiparallel P sheet of eight strands can be built up only by hairpin and/or Greek key motifs, if the connections do not cross between the two ends of the p sheet. 

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. 

Most p-independent terminators have two distinguishing features. The first is a region that produces an RNA transcript with self-complementary sequences, permitting the formation of a hairpin structure (see Fig. 8-2la) centered 15 to 20 nucleotides before the projected end of the RNA strand. The second feature is a highly conserved string of three A residues in the template strand that are transcribed into U residues near the 3 end of the hairpin. When a polymerase arrives at a termination site with this structure, it pauses (Fig. 26-7). Formation of the hairpin structure in the RNA disrupts several A=U base pairs in the RNA-DNA hybrid segment and may disrupt important interactions... 

A hairpin structure in bacterial mRNAs with a p-independent terminator (Fig. 26-7) confers stability against degradation. Similar hairpin structures can make some parts of a primary transcript more stable, leading to nonuniform degradation of transcripts. In eukaryotic cells, both the 3 poly (A) tail and the 5 cap are important to the stability of many mRNAs. Life Cycle of an mRNA... 

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