Related Sequences link

A special application of the peptide scan is the hybritope scan (hybrid-epitope) (44,45). In order to increase the affinity by extention of the peptide sequence in a hybritope scan, several mixtures of amino acids at positions flanking the related sequence of the protein are introduced. Another strategy to optimize a peptide scan is the so-called duotope scan (duo-epitope) (46). For a duotope scan one generates the peptide scan twice and combines the sequence of both arrays linked via a spacer, such as two -alanine molecules. In this way it is possible to avoid possible steric hindrance and to increase activity by extention of the active sequence. The pattern of such a duotope scan resembles that of a combinatorial library with the exception that each field represents a combination of two sequences rather than two amino acids. 

In addition to conventional sequence motifs (Prosite, BLOCKS, PRINTS, etc.), the compilation of structural motifs indicative of specific functions from known structures has been proposed [268]. This should improve even the results obtained with multiple (one-dimensional sequence) patterns exploited in the BLOCKS and PRINTS databases. Recently, the use of models to define approximate structural motifs (sometimes called fuzzy functional forms, FFFs [269]) has been put forward to construct a library of such motifs enhancing the range of applicability of motif searches at the price of reduced sensitivity and specificity. Such approaches are supported by the fact that, often, active sites of proteins necessary for specific functions are much more conserved than the overall protein structure (e.g. bacterial and eukaryotic serine proteases), such that an inexact model could have a partly accurately conserved part responsible for function. As the structural genomics projects produce a more and more comprehensive picture of the structure space with representatives for all major protein folds and with the improved homology search methods linking the related sequences and structures to such representatives, comprehensive libraries of highly discriminative structural motifs are envisionable. 

To explain the temperature dependence of the moduli, Gibson et al have considered that the crystalline sequences linking two or more crystal blocks act like short fibres in an aligned short fibre composite. Quantitative predictions of the temperature dependence of the axial modulus were obtained, which were in good agree.-nent with experimental data. In physical terms, the a - relaxation is considered to be a crystalline slip process and the 3 relaxation relates primarily to mobility of the non-crystalline regions. 

The World Wide Web has transformed the way in which we obtain and analyze published information on proteins. What only a few years ago would take days or weeks and require the use of expensive computer workstations can now be achieved in a few minutes or hours using personal computers, both PCs and Macintosh, connected to the internet. The Web contains hundreds of sites of Interest to molecular biologists, many of which are listed in Pedro s BioMolecular Research Tools (http // www.fmi.ch/biology/research tools.html). Many sites provide free access to databases that make it very easy to obtain information on structurally related proteins, the amino acid sequences of homologous proteins, relevant literature references, medical information and metabolic pathways. This development has opened up new opportunities for even non-specialists to view and manipulate a structure of interest or to carry out amino-acid sequence comparisons, and one can now rapidly obtain an overview of a particular area of molecular biology. We shall here describe some Web sites that are of interest from a structural point of view. Updated links to these sites can be found in the Introduction to Protein Structure Web site (http // WWW.ProteinStructure.com/). 

The galactose, arabinose and xylose transporters of E. coli The bacterium E. coli possesses at least 7 proton-linked, active transport systems for sugars (for a recent review see [212]). Three of these transporters, which catalyze the uptake of L-arabinose, D-xylose and D-galactose by symport with protons, are related in sequence to the sugar transporters discussed above. They probably represent the best-characterized of the non-mammalian transporters, and so are discussed here in some detail. 

The lactose transporter (lac permease) of E. coli is without doubt the most intensively studied and best understood of the bacterial proton-linked sugar transporters. Since its sequence was reported in 1980 [233] prodigious efforts have been made to elucidate its molecular mechanism by site-directed mutagenesis and other means. These studies have recently been reviewed elsewhere [234,235] and so will not be discussed in detail here. The important question for the present Chapter is whether the protein is related to the sugar-transporter family and so has lessons to teach us about their mechanisms. The permease is a 417-residue protein, and, like the other... 

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