Major groove binding

Figure 8.22 The lac repressor molecule is a V-shaped tetramer in which each arm is a dimer containing a DNA-hinding site. The helix-tum-helix motifs (red) of each dimer bind in two successive major grooves and the hinge helices (purple) bind adjacent to each other in the minor groove between the two major groove binding sites. The four subunits of the tetramer are held together by the four C-terminal helices (yellow) which form a four helix bundle. The bound DNA fragments are bent. (Adapted from M. Lewis et al., Science 271 1247-1254, 1996.)...

Some purely major groove-binding TFs, such as the basic-region leucine zipper (bZIP) protein GCN4, can co-occupy the DNA helix in the presence of polyamides [72]. Modified polyamides with an attached Arg-Pro-Arg tripeptide can interfere with major groove-binding proteins by disrupting key phosphate contacts, distort-... 

Bremer, R. E., E.E. Baird, and P.B. Dervan. Inhibition of major-groove-binding proteins by pyrrole-imidazole polyamides with an Arg-Pro-Arg positive patch. 

Antimalarial agents of the same class have been reported. Although they showed only limited anti-malarial activity, they were strong DNA-binders. They have two cationic side chains enhancing the major groove binding (69, Figure 9). ... 

A study of the mechanism of repair and cytotoxicity of 5-fluorouracil demonstrated that base excision repair by UNG is the major repair mechanism, but that cytotoxicity resulted primarily from its incorporation into RNA. Using CD spectroscopy, a novel major groove binding motif has been identified in which Zn(II) ions stabilise DNA containing 5-fluoro-5-Iodouracil is frequently used as a crosslinking agent, and has been used to map DNA binding sites in the Tetrahymena telomerase and in the telomerase ribonucleoprotein. ... 

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