Reverse turn

An important conformational feature of globular proteins are the reversetums P-tums and P-bends. They occur at hairpin corners, where the peptide chain changes direction abruptly. Such comers involve four amino acid residues often including proline and glycine. Several types of turns are known of greatest importance are type I (42% of 421 examined turns), type II (15%) and type in (18%) see Fig. 1.24. 

In type I, all amino acid residues are allowed, with the exception of proline in position 3. In type II, glycine is required in position 3. In type III, which corresponds to a 310-helix, all amino acids are allowed. The sequences of the P-bends of lysozyme are hsted in Table 1.22 as an example. 

Analysis of known protein stmctures has demonstrated that regular elements can exist in combined forms. Examples are the coiled-coil a-helix (Fig. 1.25, a), chain segments with antiparallel P-stmctures (P-meander stmcture Fig. 1.25, b) and combinations of a-helix and P-stmcture (e. g., PaPaP Fig. 1.25 c). 

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The reverse turn as a polypeptide conformation in globular proteins. Proc. Natl. Acad. Sci. USA 70 538-542, 1973. 

Umdeutung, /. reinterpretation, umdrehbar, a. reversible turning, revolving, umdrehen, v.t. r. turn roimd, rotate, twirl, twist, revolve. — umdrehend, p.a. rotatory revolving. 

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). 

Haque TS, Little JC, Gellman SH (1994) Mirror-image reverse turns promote beta- hairpin formation. J Am Chem Soc 116 4105 106... 

In most cases, pyrazino[l,2- ]pyrazines have been synthesized as highly saturated derivatives with the aim of preparing conformationally restricted compounds which mimic the secondary structure of reverse-turn regions of peptides and proteins. The saturated pyrazino[l,2- ]pyrazine 241 was synthesized from readily available starting materials, the key steps being the preparation of the keto amide 239 and subsequent tandem cyclizations from [6+0] atom fragments (Scheme 42) <20000L301>. 

E. Hisl 11 and Alai 17 Interaction May Enhance Reverse-Turn Conformation... 

The NMR data (James et al., 1997 Liu et al., 1999) show a slight reverse turn in the HI domain, similar to that proposed from X-ray diffraction (Inouye and Kirschner, 1998) however, NMR indicates that the turn is close to Alai 17. A molecular dynamics study of the helix-coil transition of PrP106—126 (Levy et al., 2001) indicates that the turn is near Alai 15, such that Hislll would interact with Vall22 rather than with Alall7. The HI domain, initially modeled as an z-helix. also adopts a /Miairpin fold as shown by molecular dynamics simulation (Daidone et al., 2005). 

Polyglutamine Huntingtin Reverse-turn /1-sheet Sharma et al. (2005)... 

Bond, J. P., Deverin, S. P., Inouye, H., el-Agnaf, O. M., Teeter, M. M., and Kirschner, D. A. (2003). Assemblies of Alzheimer s peptides A beta 25—35 and A beta 31-35 Reverse-turn conformation and side-chain interactions revealed by X-ray diffraction./. Struct. Biol. 141, 156-170. 

Demchuk E., Bashfoed D. and Case D. A. Dynamics of a type VI reverse turn in a linear peptide in aqueous solution. Fold. ... 

Glycine (Gly or G) (aminoacetic acid, aminoethanoic acid) is a nonpolar, neutral, aliphatic amino acid with the formula HOOCCH(NH2)H. Gly is the simplest amino acid and plays important roles in peptide and protein chains. It does not contain a side chain and can thus fit into secondary structures where larger amino acids cannot. Gly acts as a transmitter in the CNS where it accomplishes several functions. Gly is a precursor of porphyrins. Gly, Pro, aspartate, Ser, and Asn enable reverse turns. The acylated amino group of Gly can accept a second acyl group to give rise to a diacylamide. ... 

Slomczynska, U., Chalmers, D.K., CORNILLE, F., Smythe, M.L., Beusen, D.D., Moeller, K.D., Marshall, G.R. Electrochemical cyclization of dipeptides to form novel bicyclic, reverse-turn peptidomimetics. 2. Synthesis and conformational analysis of 6,5-bicyclic systems./. Org. Chem. 1996, 63(4), 1198-1204. 

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