Supersecondary structure

Y Cm, RS Chen, WEI Wong. Protein folding simulation with genetic algorithm and supersecondary structure constraints. Proteins 31 247-257, 1998. 

Simple combinations of a few secondary strucfure elements with a specific geometric arrangement have been found to occur frequently in protein structures. These units have been called either supersecondary structures or motifs. We will use the term "motif" throughout this book. Some of these motifs can be associated with a particular function such as DNA binding others have no specific biological function alone but are part of larger strucfural and functional assemblies. 

Ghisolfi L, Joseph G, Amalric F, Erard M (1992a) The glycine-rich domain of nucleolin has an unusual supersecondary structure responsible for its RNA-hehx-destabihzing properties. J Biol Chem... 

The helix-turn-helix scaffold is designed to dimerize into a four-helix bundle. Modification of the peptide with the nicotinoyl functionality did not significantly perturb the peptide structure. CD spectroscopy showed no loss in helici-ty from the parent peptide and NMR spectroscopy confirmed successful incorporation of the nicotinoyl group as well as maintenance of crucial NOE connectivities. In particular, the presence of long-range NOE signals between the side chains of phenylalanine 38 and leucine 12 or isoleucine 9, which lie near the C- and AT-termini, respectively, demonstrate that the supersecondary structure of the motif has been conserved. 

The size and complexity of the motif is clearly important, single hehces are of limited use because of the long intra-residue distances on the helical surface (Fig. 2) and functions that require more than two-residue sites will most hkely have to depend on the functionahzation of supersecondary structures. The clever designs of catalysts for decarboxylation and hgation reactions are, on the other hand, good examples of how small motifs can be exploited for complex functions [11,12]. 

Supersecondary structures, also called motifs or simply folds, are particularly stable arrangements of several elements of secondary structure and the connections between them. There is no universal agreement... 

The complex structures of globular proteins can be analyzed by examining stable substructures called supersecondary structures,... 

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. 

Supersecondary structures (motifs) are produced by packing side chains from adjacent secondary structural elements close to each other. 

To expand the utility of the hydrogen bond mimic, J (23) has been modified to allow for extension from the N-terminus of a hydrazone-linked cyclic peptide 148 This allows not only the use of the hydrogen bond mimic in preparing internal loops, but also the positioning of a helix nucleation site between two peptides to form supersecondary structures. To accomplish this, an a-amino group can be added to J to give J (26) (Scheme 14). Incorporation of linker J into a nucleation site using the procedure applied to 23 allows it to mimic an N-cap formed... 

Frequently recurring substructures or folds are collectively termed supersecondary structures or motifs. These are combinations of a and/or j8 structure. A simple example is a /8 hairpin, consisting of two antiparallel strands joined by a loop of three to five residues (Figure 1.12). This frequently occurs in antiparallel P sheet. Such sheet frequently contains four p strands connected as in Figure 1.13 in a motif called a Greek key (or meander, which is the Greek word for the pattern) because it is reminiscent of the Greek decorative motif, or six strands described as a jellyroll. 

Superoxide dismutase 166 Supersecondary structure 9, 20 Surface charge of protein 179-180,... 

Miles, M.J., Carr, H.J., McMaster, T.J., I Anson, K.J., Belton, P.S., Morris, V., Field, J.M., Shewry, P.R., Tatham, A.S. 1991. Scanning tunneling microscopy of a wheat seed storage protein reveals details of an unusual supersecondary structure. Proc Natl Acad Sci USA 88 68-71. 

In the complete structure, secondary-structured regions are assembled into compact units. The interactions between secondary structural units seem to be stereochemically specific. This is called the tertiary structure of the protein. (Certain common patterns of interaction between secondary structural units are known as supersecondary structures.)... 

Investigations of static structures include architectural descriptions, comparisons and classifications, and identifications of recurrent patterns such as supersecondary structures. Examples include the classification of types of proteins by Levitt and Chothia (28), the hierarchical analysis of protein structures by Rose (29), or the comparison of globin structures by Lesk and Chothia (30). 

High resolution X-ray analysis of protein structures shows that the conformational categories of the connecting peptides which link the a-helices and -sheets are limited. Such well defined types of folding units, such as aa- and PP-hairpins, and aP- and Pa-arches, are referred to as supersecondary structures. One important step towards building a tertiary structure from secondary structures is to identify these supersecondary structure... 

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