Minor groove in DNA

Figure 7.5 Schematic diagram illustrating the major and minor grooves in A- and B-DNA.

The polypeptide chain of the lac repressor subunit is arranged in four domains (Figure 8.21) an N-terminal DNA-hinding domain with a helix-turn-helix motif, a hinge helix which binds to the minor groove of DNA, a large core domain which binds the corepressor and has a structure very similar to the periplasmic arablnose-binding protein described in Chapter 4, and finally a C-terminal a helix which is involved in tetramerization. This a helix is absent in the PurR subunit structure otherwise their structures are very similar. 

Figure 8.23 The helix-turn-helix motifs of the subunits of both the PurR and the lac repressor subunits bind to the major groove of DNA with the N-terminus of the second helix, the recognition helix, pointing into the groove. The two hinge helices of each arm of the V-shaped tetramer bind adjacent to each other in the minor groove of DNA, which is wide and shallow due to distortion of the B-DNA structure. (Adapted from M.A. Schumacher et al.. Science 266 763-770, 1994.)...

The DNA helix has major and minor grooves Z-DNA forms a zigzag pattern B-DNA is the preferred conformation in vivo Specific base sequences can be recognized in B-DNA Conclusion Selected readings... 

B. H. Geierstanger, D. E. Wemmer, and P. B. Dervan. Antiparallel side-by-side dimeric motif for sequence-specific recognition in the minor groove of DNA by the designed peptide 1-methylimidazole-2-carboxamide netropsin. Proc. Natl. 

Dervan. Expanding the recognition of the minor groove of DNA by incorporation of / -alanine in hairpin polyamides. 

Swalley, S.E., E.E. Baird, and P.B. Dervan. A pyrrole-imidazole polyamide motif for recognition of eleven base pair sequences in the minor groove of DNA. Chem.-Eur. J. 1997, 3, 1600-1607. 

Dervan. Tandem hairpin motif for recognition in the minor groove of DNA by pyrrole-imidazole polyamides. Chem.-Eur. 

An analysis of the hydration structure of water molecules in the major and minor grooves in B-DNA has shown that there is a filament of water molecules connecting both the inter and the intra phosphate groups of the two strands of B-DNA. However, such a connectivity is absent in the case of Z-DNA confirming earlier MC simulation results. The probability density distributions of the counterions around DNA shows deep penetration of the counterions in Z-DNA compared to B-DNA. Further, these distributions suggest very limited mobility for the counterions and show well defined counter-ion pattern as originally suggested in the MC study. 

TBP binds to the TATA box in the minor groove of DNA (most transcription factors bind in the major groove) and causes an approximately 100-degree bend or kink of the DNA helix. This bending is thought to facilitate the interaction of TBP-associated factors with other components of the transcription initiation complex and possibly with factors bound to upstream elements. Although defined as a component of class II gene promoters, TBP, by virtue of its association with... 

Hoechst 33342 [2 -(4-ethoxyphenyl)-5-(4-methyl-l-piperazinyl)-2,5 -bi-IH-benzimidazole Ho342 I], a bisbenzimidazole dye, binds to adenine/thymine-rich regions in the minor groove of DNA. This dye induces apoptosis and inhibits topo 1 activity in vivo. It has been suggested that the destruction of immunoreactive topo I and topo I-DNA complexes or cleavable complexes results in inhibition of topo I activity, a key step in the Hoechst 33342-induced apoptotic process [40]. 

The most important aspect of coralyne is its ability to inhibit DNA relaxation in a fashion significantly similar to the most potent antitumour alkaloid camptothecin, which is known to exert this property [242], Presumably, the most notable biological action of these alkaloids appears to be topoisomerase inhibition [238-242], which has direct relevance to their DNA intercalating property. In this context. Pilch et al. [167] described a mixed binding mode model (Fig. 16) in which the protoberberine structure constitutes portions that can intercalate or bind to the minor groove of DNA. Wang et al. [240] demonstrated that coralyne (Ci) and several of its derivatives (Ce to Ch) (Scheme 5), including the partial saturated... 

Figure 11. An externally bound BPDE l(+)-N2(G) adduct, (upper) The pyrene is placed in the major groove after an anti - syn rotation about the glycosidic bond of G by 200° in an otherwise B-DNA conformation. (lower) The pyrene moiety is placed in the minor groove in a DNA conformation with a -70° kink, a(BPDE) = 15° and y(DNA = 35°.

Some of the best characterized ligands that bind in the minor groove of DNA are distamycin and netropsin. Both these molecules are long and flat and are sterically and electrostatically complementary to the characteristics of the minor groove of DNA. Distamycin and netropsin are known to have specific affinity towards the minor groove of AT rich regions of B-DNA. 

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