Reverse turns amino acid residues

Optimal pre-organization of the y-peptide backbone towards the formation of open-chain turn-like motifs is promoted by unlike-y " -amino acid residues. This design principle can be rationalized by examination of the two conformers free of syn-pentane interaction (f and II", Fig. 2.34). Tetrapeptide 150 built from homo-chiral unlike-y -amino acid building blocks 128e has been shown by NMR experiments in pyridine to adopt a reverse turn-like structure stabilized by a 14-mem-bered H-bond pseudocycle [202] (Fig. 2.37 A). 

Another change that is commonly made in peptides is the reversal of the chirality of one or more amino acid residues (reviewed in Rose et al., 1985). This is a particularly popular modification, because protected d-amino acids are commercially available, and the resulting analogs, if active, would have enhanced stabilities to enzymatic degradation. The chirality of the amino acids in the central two positions (/ + 1 and i + 2) of a turn have a profound effect on the type of turn that is formed. If the central two residues are both of the l configuration, a type I turn is often formed. If the residue at position + 1 is l and that at position i + 2 is d (an l, d pair) then a type II turn is stabilized, while a d, l pair at the central position will stabilize a type II turn (Rose et al., 1985). For this reason, type II turns are often referred to as l, d turns and type II turns as d, l turns. 

The P turn (Fig. 2-24) is often found in hairpin or reverse turns at the edges of p sheets (Fig. 2-11) and at other locahons. ° If all four residues thaf confribufe to p bends are counted, they constitute about one-third of the amino acid residues in most proteins. " In many p turns, the C=0 of the first residue hydrogen bonds to the NH of the fourth residue. This hydrogen bond may be part of the hydrogen bond network of a P pleated sheet. The peptide unit between a-carbon atoms 2 and 3 of the turn is perpendicular to the sheet. There are two possibilihes for the orientahon of fhis pephde unit. In a type I turn, the C=0 is down when the turn is viewed as in Fig. 2-24, while the side chains of residues 2 and 3 point upwards or outward on the opposite side of the bend. In a type II turn, the C=0 is up and the NH down. Residue 3 is always glycine in a type II turn because the side chain would collide with the C=0 group if any other amino acid were present. As is seen in Fig. 2-24, a frans-proline can fit at posihon 2 in a type II turn ° as well as in type I turns. A cis-proline residue can fit at position 2 or posihon 3 in a type I p 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]. 

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. 

If one of the amino acid residues in a reverse turn has a configuration different from that of the other residues, then the hydrogen bond formed is more kable. In proteins and in the majority of biologically active peptides (which are usually cleavage products of proteins) only L-residues are present, but in microbial peptides D-residues are quite common. It is not surprising, therefore, that most of them have cyclic structures ring closure is very much facilitated by reverse turns. 

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