Nonrepetitive

Other approaches to de novo four-helix bundle proteins have emphasized nonrepetitive designs. One such example is the four-helix bundle protein Felix (53), a 79-residue protein which uses 19 of the 20 naturally occurring amino acids ... 

Nonrepetitive but well-defined structures of this type form many important features of enzyme active sites. In some cases, a particular arrangement of coil structure providing a specific type of functional site recurs in several functionally related proteins. The peptide loop that binds iron-sulfur clusters in both ferredoxin and high potential iron protein is one example. Another is the central loop portion of the E—F hand structure that binds a calcium ion in several calcium-binding proteins, including calmodulin, carp parvalbumin, troponin C, and the intestinal calcium-binding protein. This loop, shown in Figure 6.26, connects two short a-helices. The calcium ion nestles into the pocket formed by this structure. 

Although the solid-phase technique was first developed for the synthesis of peptide chains and has seen considerable use for this purpose, it has also been used to synthesize chains of polysaccharides and polynucleotides in the latter case, solid-phase synthesis has almost completely replaced synthesis in solution. The technique has been applied less often to reactions in which only two molecules are brought together (nonrepetitive syntheses), but many examples have been reported. 

The DNA in a eukaryotic genome can be divided into different sequence classes. These are unique-sequence, or nonrepetitive, DNA and repetitive-sequence DNA. In the haploid genome, unique-sequence DNA generally includes the single copy genes that code for proteins. The repetitive DNA in the haploid genome includes sequences that vary in copy number from two to as many as 10 copies per cell. 

More Than Half the DNA in Eukaryotic Organisms Is in Unique or Nonrepetitive Sequences... 

AEGL Acute Exposure Guideline Levels describe the risk from single, nonrepetit-ive exposures to airborne chemicals in a once-in-a-lifetime event. They represent... 

Based on the same principle, there are monomeric / -helical proteins that carry at their extremities a cluster of helical or nonrepetitive structures that could act as a capping element covering their exposed ends (Emsley et al., 1996 Lietzke et al, 1994 Petersen et al, 1997 Steinbacher et al, 1994). For example, the last 40 residues of pectate lyase C form a large loop that partially covers the surface of the /Hielix (Yoder et al, 1993). The fibrous (or otherwise elongated) domain of these natural /f-stranded proteins is not stable in isolation, as for example in the case of the P22 tailspike where bacterially expressed isolated /Hielix domain, at high concentrations, forms fibrous aggregates that bind Congo red (Schuler et al, 1999). 

In contrast to the well-ordered but nonrepetitive coil structures, there are also genuinely disordered regions in proteins, which are either entirely absent on electron density maps or which appear with a much lower and more spread out density than the rest of the protein. The disorder could either be caused by actual motion, on a time scale of anything shorter than about a day, or it could be caused by having multiple alternative conformations taken up by the different mole-... 

Approximately one half of an average globular protein is organized into repetitive structures, such as the a-helix and/or 3-sheet. The remainder of the polypeptide chain is described as having a loop or coil conformation. These nonrepetitive secondary structures are not... 

Globular proteins are constructed by combining secondary structural elements (a-helices, 3-sheets, nonrepetitive sequences). These form primarily the core region—that is, the interior of the molecule. They are connected by loop regions (for example, 3-bends) at the surface of the protein. Supersecondary structures are usually pro duced by packing side chains from adjacent secondary structural elements close to each other. Thus, for example, a-helices and 3-sheets that are adjacent in the amino acid sequence are also usu ally (but not always) adjacent in the final, folded protein. Some of the more common motifs are illustrated in Figure 2.8. 

Furst, D. O., Osborn, M., and Nave, R. (1988). The organization of titin filaments in the half-sarcomere revealed by monoclonal antibodies in immunoelectron microscopy A map of ten nonrepetitive epitopes starting at the Z line extends close to the M line. J. Cell. Biol. 106, 1563-1572. 

Figure 2 Schematic representation of the repetitive structure of (a) fibroin (Sehnal and Zurovec, 2004), (b) the crystalline and amorphous regions in silk, and (c) the structure of the parallel P-sheet crystals (Zhou et al., 2001). The bullnose symbols in (a) depict the nonrepetitive termini. Each pair of rectangle and triangle represents a second-order repeat unit. Each line on the symbols is the unit of third-order repeat. Crystalline regions are shown in black (Gosline et al., 1986 Heslot, 1998).

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