Sequence-Dependent Motifs

S ETdomain containing H KMTs have been classified according to the presence or absence and the nature of the sequences surrounding the SET domain that are conserved within families [71, 72]. The SET domain has a unique structural fold classified as class V AdoMet-dependent methyltransferase (MTase) [69], characterized by four highly-conserved signature sequences, namely motif I... 

Early work in the field has established the synthetic strategies and analytical tools for such class of libraries (for reviews see refs[111 112 456]). As listed in Table 13, the first generation of cyclic peptide libraries focused on biologically active sequences such as the cell adhesion RGD motif, the antileukemic heptapeptide stylostatin, or endothelin antagonists, but also on metal-binding sequence motifs and on the de novo discovery of bioactive cyclic peptides without sequence-biased motifs. Moreover, synthetic questions were addressed such as the sequence dependency of peptide cyclization reactions (see Table 13). 

In recent years an astonishing structural variety has been rmcovered for DNA. Crystal structures have shown that, apart from the structural motifs of the A-, B- and Z-forms of DNA, other, sequence-dependent structural variations exist which are observed when smaller sequence fragments are examined in detail. 

A. oryzae a-amylase consists of three domains (A, B and C).179,180 Domain A has an amino-terminal ((3/a)8-barrel structure, followed by domain C, consisting of (3-strands that are folded into a Greek motif. Domain B is inserted between the third (3-strand and the third a-helix of the ((3/a)8-barrel. This is a highly variable domain in both its length and amino acid sequence, depending on the source and type of the enzyme.181,182 Cyclomaltodextrin glucanosyltransferases generally consist of five domains (A, B, C, D and E). Domains A, B and C consist of the same catalytic domains found in... 

In recent years, as the size of the PDB has increased, database methods have continued to attract attention. With a larger database, recurring structural motifs have been classified for loop structures [111, 114, 116, 129, 134], including their sequence dependence. Database methods have been applied only for loops of up to 8 residues. Fidelis et al. [126] found that for loops of length greater than 7 there is not likely to be a segment in the PDB that corresponds to the correct loop conformations for the 58 protein they looked at. Some authors report that when the database contains a loop of similar structure to the target to be modeled, their methods perform well, with RMSD values around 1A or better. Otherwise they tend to fail [124, 127, 130]. 

You can often think of motif discovery as a needle-in-a-haystack problem where the motif is the needle and the sequences in which it is embedded is the haystack. Because motif discovery algorithms depend on the relative over-representation of a motif in the input set of sequences, a motif is weak if it is not significantly over-represented in the input sequences relative to what is expected by chance (or relative to a negative set of sequences) (71). 

Sequence-dependent toxicity Palindromic sequences and dinucleotide motifs containing CpG sequences in particular, have been shown to posses potent immunostimulatory properties in rodents. Similar effects do not seem to occur in primates. 

LNA has been used in a variety of other biological applications. LNA, and its 2 -amino analogue, has been incorporated into aptamers (see section 2) for enhanced binding affinity." LNA has been substituted into i-motif structures, where it can have a significant effect on the structural stability. The presence of LNA in the structure alters the stability of the hemiprotonated cytosine base pairs, and as there is a sequence effect it is possible to tune the stability of the i-motif." Substituting LNA into quadruplex structures also has a sequence-dependent effect on stability, where in only certain positions are well-defined structures obtained." More recently the use of LNA nucleotides as polymerase substrates has been examined." KOD DNA polymerase has been shown to be a useful polymerase for the incorporation of LNA triphosphates into DNA, including its use as the polymerase in PCR reactions with LNA modifications." ... 

Peptides adsorbed at membrane surfaces share a common characteristic - the anisotropic interfacial environment exerts an organizing effect on their structure. Even though in the nonassociated form they are disordered in aqueous solution, they can adopt sequence-dependent, ordered structures at interfaces. All major structural motifs found in proteins, such as a-helices, -strands, and )5-tums, were observed experimentally in membrane-bound, natural, or synthetic peptides. 

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