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Dynamical Features of Cognate Site Recognition in bZIP-DNA Interaction
Published in American Chemical Society
Volume: 4
Issue: 1
Pages: 292 - 308
The prototypical basic leucine zipper (bZIP) transcription factor GCN4 from yeast binds to the ATF/CRE DNA sequence with high affinity. It has been observed that while the symmetric replacement of cytosine at the 2′ position of both the strands of the hexameric core by guanine or thymine is strongly disfavored, the replacement by adenine is relatively less so. We report here results from molecular dynamics simulations that revealed a nearly identical polypeptide backbone conformation and dynamics in the cognate and the three noncognate complexes which differ by only one substitution from the cognate half-site, as assessed by a backbone order parameter and secondary structure analysis. However, our calculations identified significant perturbations in the side-chain dynamics of the highly conserved asparagine residues, which showed a close correlation with the loss of base-specific interactions. Examination of the role of interfacial water molecules revealed a loss of several water-mediated hydrogen bonds in the substituted CRE-GCN4 complexes. We observed a significant increase in the SASA values for the mutated DNA sites, indicating an overall loosening in the noncognate complexes which may facilitate movement of the protein along the DNA. However, no enhanced rotational fluctuation of the protein about the DNA was observed. © 2019 American Chemical Society.
About the journal
JournalData powered by TypesetACS Omega
PublisherData powered by TypesetAmerican Chemical Society
Open AccessNo