Date of Award
2023
Document Type
Thesis
Degree Name
Master of Science (M.S.)
Department
Pharmaceutical and Chemical Sciences
First Advisor
Jerry Tsai
First Committee Member
Joseph Harrison
Second Committee Member
Liang Xue
Abstract
To investigate whether higher order packing interactions confer protein-DNA specificity, a modified Knob-Socket (KS) model was used to analyze the interface of bZIP-DNA crystal structures. The KS analysis identified a nine-residue quadripartite recognition core consisting of four contiguous KS pockets P1, P2, N3, and N4 that each pack one of the four DNA half-site bases in the target sequence. Only one base per base pair packs, and these interactions are split across the DNA strands: the first two positive strand positions 1p and 2p pack into P1 and P2 while the last two negative strand positions 3n and 4n pack into N3 and N4. Amino acid sequence analysis of the four KS pocket regions indicates that the primary mechanism recognition is packing or non-packing of the 5-methyl group of dT as well as 5-methylcytosine. P1 shows little packing of dT; P2 packs dT but including two Asn residues in this pocket seems to block packing in this region; N3 also packs dT, but including a Phe also blocks packing; N4 consistently packs dT. This analysis demonstrates that there is an amino acid code to DNA recognition, allowing for multi-residue recognition and packing of the 5-methyl group.
Pages
121
Recommended Citation
Tran, Aaron. (2023). Investigating bZip Recognition of DNA Sequences Through a Knob-Socket Perspective. University of the Pacific, Thesis. https://scholarlycommons.pacific.edu/uop_etds/4173
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