Binding in The Major Groove

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Introduction

HTH Motif

Major Groove

N-termnal Arm

Conclusions

References

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Helix 3 is the helix responsible for the majority of DNA binding of the HTH motif. Its binding to DNA is complemented by binding of other residues located in the N-terminal arm and residues located down sequence form Helix 3 in the primary protein sturcture. The contributions of each will be examined respectively.

Important DNA Contacts of Helix 3:

As mentioned before, helix 3 is responsible for the site specific recognition of DNA binding. This helix lies in the major groove of the DNA to which it is bound. Gln44 and Ser45 both form H-bonds to the operator site.

Gln44

The first amino acid of helix 3 is Gln44. Gln first contacts are with thymine and adenine, the first and second base pairs of the consensus operator sequence respectively. Gln44's side chain NH2 donates an H-bond to the N-7 of adenine and, its side chain oxygen accepts an H-bond from the N-6 of adenine. In addition to forming hydrogen bonds, the delta- and gama-carbon groups of Gln44 have Van der Waals' contacts with the thymine methyl group of base pair 1.

Ser45

Ser45 is the second residue of helix 3. Ser45 makes contacts with thymine and guanine, the third and fourth base pairs of the consensus operator sequence respectively. Ser45 is an H-bond donor to either the N-7 or O-6 of guanine. Close up of H-bonding interactions. Van der Waal's interactions that the alpha- and beta-carbons of Ser45 make to the methyl group of thymine are important for recognition on the consensus half. Water mediated H-bonding also occurs between the backbone carbonyl of Ser45 and the N-4 of cytosine 4 and the O-4 of thymine 5. This is the only conformation Ser45 can have in the consensus operator half site. In the non-consensus half site, Ser45 can go between two different conformations. In one, it makes approximately the same contacts as in the consensus half site. The second conformation allows Ser45 to form a H-bond to N-4 of cystine. This base pair is the third base pair in the non-consensus half site.