Intercalating residues

In addition to the kink induced by the primary intercalating residue, a second kink two base steps away from the primary kink is revealed in the crystal structure of a complex of the HMG-D box with linear DNA [32]. The second kink arises from partial secondary intercalation in the minor groove of two adjacent residues, valine and threonine, immediately before the N-terminal end of helix II [32,42]. In the HMG boxes of HMGBl and 2, and other non-sequence-specific HMG proteins, a hydrophobic (and therefore potentially intercalating) residue is almost always found in the position corresponding to the valine in HMG-D [32,42] (residue Y in Table 1 and Fig. 2). In contrast, in the sequence-specific HMG... 

The basis of the preference of the A domain, relative to the B domain, of HMGBl for binding to distorted DNA structures has become apparent from numerous structural and biophysical studies. In contrast to the B domain, the A domain has only the secondary potentially intercalating residue, namely Phe at position Y (Table 1 and Fig. 2). This presumably accounts for the smaller bend angle in the A domain/cisplatin-modified DNA eomplex (61°) than in the B domain complex (80-95°) [34,43]. As yet, there is no strueture of a complex between the A domain and linear DNA. However, in the erystal structure of the A domain complexed with cisplatin-modified DNA the domain binds to one side of the cA-platinum adduet. 

He, Q., Ohndorf, U.M., and Lippard, S.J. (2000) Intercalating residues determine the mode of HMGl domains A and B binding to cisplatin-modified DNA. Biochemistry 39, 14426-14435. 

Hydrophobic bonds, or, more accurately, interactions, form because nonpolar side chains of amino acids and other nonpolar solutes prefer to cluster in a nonpolar environment rather than to intercalate in a polar solvent such as water. The forming of hydrophobic bonds minimizes the interaction of nonpolar residues with water and is therefore highly favorable. Such clustering is entropically driven. The side chains of the amino acids in the interior or core of the protein structure are almost exclusively hydrophobic. Polar amino acids are almost never found in the interior of a protein, but the protein surface may consist of both polar and nonpolar residues. 

Experimental results now suggest that the intercalant species in residue compounds may be ordered (S31,13, CIO). Detailed electron-... 

The psoralen ring system can intercalate within double-stranded DNA or RNA and induce the formation of adducts with adjacent thymine bases (Figure 11.15). The furan-side and pyrone-side of the tricyclic rings in psoralen both can form cycloaddition products with the 5,6-double bond of thymine residues, which results in crosslinks between the DNA strands with a PEG-biotin label sticking out. 

Fig. 20. Molecular models of two conformers of 14-mer duplex d(ATACATGGTACATA) ruthenated at N7 of one of the guanine residues with [Ru(ri6-bip)Cl(en)]+ (10). Conformer (a) shows the intercalation of the arene (b) shows the nonintercalated phenyl ring of the arene stacked on a thymine residue.

---