Major groove sequence-specific recognition

Figure 7.8 Sequence-specific recognition sites in the major groove of DNA for three restriction enzymes—Eco RI, Bal I, and Sma I. The DNA sequences that are recognized by these enzymes ate represented by tbe color code defined in Figure 7.7.

Most sequence-specific regulatory proteins bind to their DNA targets by presenting an a helix or a pair of antiparallel p strands to the major groove of DNA. Recognition of the TATA box by TBP is therefore exceptional it utilizes a concave pleated sheet protein surface that interacts with the minor groove of DNA. Since the minor groove has very few sequence-specific... 

S. Yoshizawa, D. Fourmy, R. G. Eason, and J. D. Puglisi, Sequence-specific recognition of the major groove of RNA by deoxystreptamine. Biochemistry, 41 (2002) 6263-6270. 

DNA. By far, the most common secondary structure for DNA is the double helix. Sequence-specific recognition of double-helical DNA relies on several factors. First, the array of fimctional groups exposed in the major and minor grooves can be read by DNA-binding ligands. This is referred to as direct readout. However, more subtle factors may also be involved, such as sequence-dependent variation in the shape, flexibility, and hydration of the DNA. Ligands which discriminate among sequences based on these parameters utilize indirect readout of the sequence information. 

Drugs that bind to DNA may occur on the major groove face, minor groove face or a combination. The grooves are excellent sites for sequence specific recognition since there are... 

Bacteriophage repressor proteins provide excellent examples of sequence-specific interactions between the side chains of a protein and bases lining the floor of the major groove of B-DNA. As we shall see, to fit the protein s recognition module into this groove it has to be made even wider in other words, the B-DNA has to be distorted. 

Figure 9.10 Schematic diagrams illustrating the complex between DNA (orange) and one monomer of the homeodomain. The recognition helix (red) binds in the major groove of DNA and provides the sequence-specific interactions with bases in the DNA. The N-terminus (green) binds in the minor groove on the opposite side of the DNA molecule and arginine side chains make nonspecific interactions with the phosphate groups of the DNA. (Adapted from C.R. Kissinger et al Cell 63 579-590, 1990.)...

Figure 10.11 Sequence-specific interactions between DNA (yellow) and the recognition helix (red) of the glucocorticoid receptor. Three residues, Lys 461, Val 462 and Arg 466 make specific contacts with the edges of the bases In the major groove.

Three residues. His 28, Glu 32 and Arg 36, form specific interactions with the edges of the bases in the major groove of DNA. Like MyoD, a Glu residue recognizes the first two bases, C and A, of the recognition sequence. 

Fig. 1.5. Zif268 in complex with DNA. a) specific H-bonds between amino add side chains of fingers 1-3 of Zif268 and bases of the recognition sequence. The DNA is drawn as cylinders. The arrows emphasize contact with the major groove, b) periodic arrangement of fingers in the major groove of the DNA. According Pabo and Sauer (1992), with permission.

The leucine zipper itself does not participate in the recognition it is only utilized for dimerization of the proteins. The N-terminal end of the basic leucine zipper motif is relatively unstructured in the absence of DNA. A helical structure is induced upon binding to DNA allowing specific contacts to the recognition sequence. Dimer formation is a prerequisite for the exact positioning of the N-terminal basic end in the major groove of the DNA. Analogous to the dimeric structure of the protein, the DNA sequence displays 2-fold synunetry (see 1.2.4). 

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