Proteins reverse turns

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

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>. 

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. ... 

Secondary structure refers to regularities or repeating features in the conformation of the protein chain s backbone. Four major types of secondary structure in proteins are (1) the alpha (a) helix, formed from a single strand of amino acids (2) the beta (P) sheet, formed from two or more amino acid strands (from either the same chain or from different chains) (3) the beta (P) bend or reverse turn, in a single strand and (4) the collagen helix, composed of three strands of amino acids. 

In addition to incorporating the 4-(2-aminoethyl)dibenzofuran-6-propanoic acid template into small peptides where a reverse turn is desired, we have also recently incorporated this template into a mini-protein called the PIN WW domain. WW domains have a three-stranded antiparallel p-sheet structure that mediates intracellular protein-protein interactions. 31 Substitution of this 3-turn mimetic into loop 1 of the PIN WW domain leads to a folded, three-stranded, antiparallel p-sheet structure with a stability indistinguishable from that of the all a-amino acid sequence. The template-incorporated PIN WW domain (11) was synthesized by an Fmoc-based solid-phase peptide synthesis strategy (Scheme 8), utilizing N-Fmoc-protected 4-(2-aminoethyl)dibenzofuran-6-propanoic acid 10. 11 The synthesis of 10, similar to that of 8, has been published.1 1 ... 

The other major protein in the extracellular matrix is elastin, which is the main component of elastic fibers found in ligaments, large arteries, and lungs. After synthesis and partial hydroxylation of proline residues, a 72 kDa molecule of tropoelastin is secreted into the matrix. This protein is rich in nonpolar amino acids and contains repeating sequences, such as (Val-Pro-Gly-Val-Gly). These sections form an amorphous, random-coiled structure with frequent reverse turns. Other recurrent sequences are rich in alanine with paired lysine residues, e.g., -Ala-Ala-Ala-Ala-Lys-Ala-Ala-Lys-... 

Both approaches are empirical. They depend on comparing unknown spectra with spectra which represent presumably known structures. They give relatively accurate percentages of helix, P-sheet, reverse turn, and unfolded structure, but quantitate only the average secondary structure content [108]. The relative success of these spectroscopic methods gives confidence that more detailed information about specific vibrational characteristics of peptides and proteins will provide valuable and useful contributions to the study of these problems. The developments... 

Table 10.1 summarizes neural network applications for protein structure prediction. Protein secondary structure prediction is often used as the first step toward understanding and predicting tertiary structure because secondary structure elements constitute the building blocks of the folding units. An estimated 90% or so of the residues in most proteins are involved in three classes of secondary structures, the a-helices, p-strands or reverse turns. Related to the secondary structure prediction are also the prediction of solvent accessibility, transmembrane helices, and secondary structure content (10.2). Neural networks have also been applied to protein tertiary structure prediction, such as the prediction of the backbones or side-chain packing, and to structural class prediction (10.3). 

Here again, not all chromatographic setups are usable for any proteomics question. The use of protein reverse phase chromatography, which has been advocated for plasma proteomics (Moritz et al. 2005), precludes in turn the use of any detergent of any type. This prevents the use of this chromatographic setup in most subcellular proteomics experiments, where detergents must be used to solubilize the membrane limiting the subcellular compartments. 

Thioredoxin from Escherichia coli is a small ubiquitous protein with of 11,700 which contains a redox-active cystine moiety on an exposed jS-reverse-turn . It can... 

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. ... 

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