Sequence specificity hydrogen bonding

The only sequence-specific hydrogen bonds between TBP side chains and the bases in the minor groove occur at the very center of the TATA box (Figure 9.7). The amide groups of two asparagine side chains donate four hydrogen bonds, two each to adjacent bases on the same DNA strand (Asn 69... 

Like Thr 124 and Thr 215, the Asn 69 and Asn 159 residues occupy equivalent positions in the two homologous motifs of TBP. By analogy with the symmetric binding of a dimeric repressor molecule to a palindromic sequence described in Chapter 8, the two motifs of TBP form symmetric sequence-specific hydrogen bonds to the quasi-palindromic DNA sequence at the center of the TATA box. The consensus TATA-box sequence has an A-T base pair at position 4, but either a T-A or an A-T base pair at the symmetry-related position 5, and the sequence is, therefore, not strictly palindromic. However, the hydrogen bonds in the minor groove can be formed equally well to an A-T base pair or to a T-A base pair, because 02 of thymine and N3 of adenine occupy nearly stereochemically equivalent positions, and it is sufficient, therefore, for the consensus sequence of the TATA box to be quasi-palindromic. 

SEQUENCE-SPECIFIC HYDROGEN BONDED UNITS FOR DIRECTED ASSOCIATION, ASSEMBLY, AND LIGATION... 

The Major and Minor Grooves Are Lined by Sequence Specific Hydrogen-Bonding Groups... 

In conclusion, one important factor that contributes to the strong affinity of TBP proteins to TATA boxes is the large hydrophobic interaction area between them. Major distortions of the B-DNA structure cause the DNA to present a wide and shallow minor groove surface that is sterically complementary to the underside of the saddle structure of the TBP protein. The complementarity of these surfaces, and in addition the six specific hydrogen bonds between four side chains from TBP and four hydrogen bond acceptors from bases in the minor groove, are the main factors responsible for causing TBP to bind to TATA boxes 100,000-fold more readily than to a random DNA sequence. 

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