Hairpin helices

Statistics of branching and Hairpin helices for dAT copolymer , BioDolvmers. 6, 715 (1968). 

Different hypotheses have been proposed for the initial structures acting as nucleation centers. These hypotheses include a compact nativelike structure occurring by a random folding (see Baldwin, 1980), a cluster of hydrophobic residues (Matheson and Scheraga, 1978 Wiithrich and Wagner, 1978), a cluster of a helices (Lim, 1978), or a cluster of P sheet hairpin helices (Ptitsyn et a/., 1979). 

At a higher level, very little information was obtained on the initial formation of segments of secondary structures, the a helices or P structures. Once formed, do they persist until the native conformation of the whole protein is achieved Or, as proposed by Ptitsyn and co-workers (1979), are the long hairpin helices formed initially Then, does a reorganization of the overall structure including the transformation of hairpin hehces into other ordered structures with different mechanisms according to the type of protein take place ... 

HhHl Helix-hairpin-helix DNA-binding motif class 1 E(MFP)AB 2(2) 2(3) 1BDX... 

HhH2 Helix-hairpin-helix class 2 (Poll family) motifs E(MFP)AB 0(0) 4(4) 1BGX... 

Flg.1. In the amino acid sequence of KO-42 is encoded its fold and its function as it controls the formation of a hairpin helix-loop-helix motif that dimerizes to form a four-helix bundle. On the surface of the folded motif a reactive site is formed that catalyzes hydrolysis, transesterification and amidation reactions of reactive esters, whereas unfolded peptides are incapable of cooperative catalysis. In addition the values, and thus the reactivities, of the histidine residues are controlled by the fold. The pK of each His residue of KO-42 is shown in the figure and deviate by as much as 1.2 units from that of random coil peptides which is 6.4... 

The 42-residue peptide KO-42 folds in solution into a hairpin helix-loop-helix motif that dimerizes to form a four-helix bundle. On the surface of the folded motif there are six histidines with assigned piC values in the range 5.2 to 7.2 (Fig. 1) and the second-order rate constant for the hydrolysis of mono-p-nitro-phenyl fumarate is 1140 times larger than that of the 4-methylimidazole-cataly-zed reaction at pH 4.1 and 290 K [13]. The reaction mechanism was found to be pH dependent as the kinetic solvent isotope effect was 2.0 at pH 4.7 and 1.0 at pH 6.1 and the pH dependence showed that the reaction rate depended on residues in their unprotonated form with piCj, values around 5. It was thus established that there are functional cooperative reactive sites that contain protonated and unprotonated His residues. 

Two classes of DNA repair enzymes contain [4Fe-4S] + clusters that are not involved in catalysis and appear to have purely structural roles. Several members of the superfamily of helix-hairpin-helix DNA repair enzymes contain a redox-inert [4Fe-4S] + cluster coordinated by a C-X6-C-X2-C-X5-C cysteine motif, for example, endonuclease in 50,5i,263 52,79,264,265 thymine-DNA... 

Hollis, T., Ichikawa, Y, and Ellenberger, T. (2000). DNA bending and a flip-out mechanism for base excision by the heltx-hairpin-helix DNA glycosylase, Escherichia coli AlkA. EMBO J. 19, 758-766. 

Fig. 4. (a) A possible configuration for a circular DNA chain with hairpin helix branching, (b) Sketch of strand sliding effect on loops of broken bonds. 

For poly d(A-T)-poly d(A-T), neglecting hairpin helix branching, we find two L, nS, Li2, and L - If we average over both of these values,... 

A proper theoretical examination of poly d(A-T)-poly [Pg.178]

Using the Un values obtained from poly d(A) poly d(T), the three models were compared with the melting curve of poly d(A-T) poly theoretical calculations included the hairpin helix effects. Equation (2.43e) is applicable to both the MI and MIS models and was employed in both cases. Uijman s equation (42) was used for the LE model. 

The comparison between theoretical models and poly helix structures must... 

Baltzer s group has recently described a fully-synthetic protein that is also capable of hydrolysing p-nitrophenyl esters the polypeptide, which contains 42 amino acids, was designed to fold into a hairpin helix-loop-helix motif that dimerises into a four-helix bundle. The dimer is predicted to present on its surface a shallow reactive site containing several histidine residues. The spectroscopic properties of the peptide are consistent with the predicted folded structure, and the molecule does indeed catalyse ester hydrolysis (and transesterification) more effectively than 4-methylimidazole does. However, there is little substrate selectivity, and not much turnover. The histidine array does not seem to act via general acid-base catalysis, but rather to bind and stabilise ester oxygens in the transition state. We return to this molecule below. 

The hairpin motif is a simple and frequently used way to connect two antiparallel p strands, since the connected ends of the p strands are close together at the same edge of the p sheet. How are parallel p strands connected If two adjacent strands are consecutive in the amino acid sequence, the two ends that must be joined are at opposite edges of the p sheet. The polypeptide chain must cross the p sheet from one edge to the other and connect the next p strand close to the point where the first p strand started. Such CTossover connections are frequently made by a helices. The polypeptide chain must turn twice using loop regions, and the motif that is formed is thus a p strand followed by a loop, an a helix, another loop, and, finally, the second p strand. 

The major stmctural feature of the HAz chain (blue in Figure 5.20) is a hairpin loop of two a helices packed together. The second a helix is 50 amino acids long and reaches back 76 A toward the membrane. At the bottom of the stem there is a i sheet of five antiparallel strands. The central i strand is from HAi, and this is flanked on both sides by hairpin loops from HAz. About 20 residues at the amino terminal end of HAz are associated with the activity by which the vims penetrates the host cell membrane to initiate infection. This region, which is quite hydrophobic, is called the fusion peptide. 

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. 

M-3/4 helix unknown 10-member turn (hairpin) P-12/10 helix /3... 

---