Problem:

Answer the following questions in detail:

Question 1: What features of the major groove make it especially useful for sequence-specific recognition by proteins? Give at least two examples of DNA-binding motifs that bind primarily to the major groove. Provide an example of a protein that does NOT use the major groove to recognize its target. How does it accomplish its specific binding?

Question 2: Address the contribution made by nonspecific contacts with the DNA backbone to the binding affinity of typical DNA-binding proteins. What constraints are imposed on a protein by relying on such contacts for sequence-specific DNA binding? What advantages are provided?

Question 3: Describe the role of water in protein structure formation.

Question 4: DNA repair proteins, such as DNA glycosylase, recognize and remove damaged nucleotides. Based on what you know about protein-DNA interactions, suggest how these repair enzymes recognize mismatches or damaged bases in double-helix DNA, and suggest what specific contacts are made between the DNA repair protein and the mismatched (or damaged) base.