Polypeptide chain reverse turn

Our next examples concern the characterization of /J-turns, which are structural elements that permit polypeptide chain reversals in proteins [65]. Tight turns in proteins and peptides, involving two residues as folding nuclei, have been widely investigated [66-69]. We have applied our GA technique for structure solution of the peptides Piv-LPro-Gly-NHMe and Piv-LPro-y-Abu-NHMe from powder diffraction data, in order to explore the structural properties of these materials (particularly with regard to the formation of /J-turns). 

A polypeptide chain can turn comers in a number of ways, to go from one segment or ot helix to the next. One kind of compact turn is called a turn (Figure 6.18). There are several varieties of turn, each able to accomplish a complete reversal of the polypeptide chain direction in only four residues the carbonyl of residue i hydrogen-bonds to the amide hydrogen of residue i + 3. 

Polypeptides and proteins can undergo other conformational changes, especially when they exist in relatively compact structures wherein the backbone can fold back on itself, or make a turn (i.e., a site where the polypeptide chain reverses its overall direction). It is these reverse turns (e.g., p-turn or hairpin bend) that afford proteins with globular properties (18). A further discussion of turns is beyond the scope of this chapter, but the interested reader can find many good discussions ofthis topic in other sources (16,19). 

On average, one third of all residues in proteins are involved in turns that serve to reverse the direction of the polypeptide chain. These turns are an essential feature of globular proteins and are almost always located at the surface. In contrast to a-helices and j8-strands which have repetitive conformational angles, the conformational angles observed in turns occur in sets that are characteristic of each type (Table 11). Turns have been classified according to the commonly observed groups of conformational angles and the number of residues involved. Of these the -hairpin or reverse turn is the most common. This type of turn is frequently used to connect antiparallel y3-strands. 

Another possibility of folding for the same end chain reversal is the y turn, in which the direction of the polypeptide chain reversed over three... 

Reversal of the chain direction corresponding to p turns are common features of globular proteins. They connect different types of structured or nonstructured segments of the polypeptide chain. Reverse chain folding is stabilized by antiparallel P sheets, helix-helix, and helix-j5-strand interactions. Isogai and co-workers (1980) described a new type of structure, referred to as the multiple bend. 

Turns are segments between secondary structural elements and are defined as sites in a polypeptide structure where the peptidic chain reverses its overall... 

The regular secondary structures, a helices and /i sheets, are connected by coil or loop regions of various lengths and irregular shapes. A variant of the loop is the f> turn or reverse turn, where the polypeptide chain makes a sharp, hairpin bend, producing an antiparallel / turn in the process. 

Other kinds of turns which are much more rarely encountered are the a-turn with l<-5 hydrogen bond which represents one single turn of an a-helix, or the three-residue y-turn with a l<-3 hydrogen bond. This latter turn produces a kink rather than a hairpin-like reversal in a polypeptide chain [596, 603], see Thble 19.5. 

Polypeptide Chains Can Change Direetion by Making Reverse Turns and Loops... 

Figure 3.42. Structure of a Reverse Tuni. The CO group of residue i of the polypeptide chain is hydrogen bonded to the NH group of residue i + 3 to stabilize the turn.

Thioredoxin from E. coli has been studied extensively using biochemical, spectroscopic and X-ray diffraction techniques. The protein consists of a single polypeptide chain of 108 amino acid residues of known sequence. The protein has been cloned and expressed. Thioredoxin of E. coli is a compact molecule with 90% of its residues in hehces, beta-strands or reverse turns. This protein transports electrons via an oxidation-reduction active disulfide". The oxidized form thioredoxin-(S2) is reduced to thioredoxin-(SH)2. In particular, this protein was found to participate in the reduction of ribonucleotides to deoxyribonucleotides. In Fig. 1, the optimized stracture is shown with a carbon backbone for clarity only. The molecule consists of two conformational domains, connected by two helices. The beta-sheet forms the core of the molecule packed on either side by clusters of hydrophobic residues. Helices form the external surface. We used a crystal stracture of the oxidized form of thioredoxin from Escherichia coli that has been refined by the stereochemically restrained least-squares procedure at 1.68 A resolution". ... 

In contrast to a-helices, /1-sheets do not involve interactions between amino acids close in sequence. Amino acids that interact within / -sheets are often found widely separated in the primary structure. Therefore, / -sheet formation needs structures that bring two polypeptide segments into close proximity. This is achieved via reverse turn structures [96]. Turns are aperiodic or nonrepetitive elements of secondary structure which mediate the folding of the polypeptide chain into a compact tertiary structure. Turns usually occur on the environment-exposed surface of proteins [97,98], Reverse turns play an important role in polypeptide function, both as elements of structure as well as modulators of bioactivity [99]. Among the reverse turns found in proteins the /1-turn is the most relevant [100]. /1-Turns comprise four amino acid residues (i to i+3) forming an almost complete 180° turn in the direction of the peptide chain [101,102]. 

Many globular proteins contain combinations of a-helix and /Tpleated sheet secondary structures (Figure 5.20). These patterns are called supersecondary structures. In the /la/1 unit, two parallel /Tpleated sheets are connected by an a-helix segment. In the fi-meander pattern, two antiparallel /1-sheets are connected by polar amino acids and glycines to effect an abrupt change in direction of the polypeptide chain called reverse or fi-turns. In aa-units, two successive a-helices separated by a loop or nonhelical segment become enmeshed because of compatible side chains. Several j8-barrel arrangements are formed when various... 

Proteins take up several different secondary structures, including the a-helix, b-sheet, and reverse turns. The shape of the polypeptide chain is constrained by the planar peptide bond and noncovalent interactions. 

They usually occur at the surface of proteins. Figure 6.18 depicts two examples of turns, which completely reverse the direction of the polypeptide chain in only four amino acid residues. This occurs via hydrogen bonding between resides 1 and 4. A tighter turn, called the 7 turn, is shown in Figure 6.19. It occurs in only 3 residues. 

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