Gary W. Daughdrill
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View article: Sequence Properties of an Intramolecular Interaction that Inhibits p53 DNA Binding
Sequence Properties of an Intramolecular Interaction that Inhibits p53 DNA Binding Open
An intramolecular interaction between the p53 transactivation and DNA binding domains inhibits DNA binding. To study this autoinhibition, we used a fragment of p53, referred to as ND WT, containing the N-terminal transactivation domains (T…
View article: Conformational buffering underlies functional selection in intrinsically disordered protein regions
Conformational buffering underlies functional selection in intrinsically disordered protein regions Open
Many disordered proteins conserve essential functions in the face of extensive sequence variation. This makes it challenging to identify the forces responsible for functional selection. Viruses are robust model systems to investigate funct…
View article: Rational Design of Right-Handed Heterogeneous Peptidomimetics as Inhibitors of Protein–Protein Interactions
Rational Design of Right-Handed Heterogeneous Peptidomimetics as Inhibitors of Protein–Protein Interactions Open
Peptidomimetics have gained great attention for their function as protein-protein interaction (PPI) inhibitors. Herein, we report the design and investigation of a series of right-handed helical heterogeneous 1:1 α/Sulfono-γ-AA peptides as…
View article: Correction to α-Helix-Mimicking Sulfono-γ-AApeptide Inhibitors for p53–MDM2/MDMX Protein–Protein Interactions
Correction to α-Helix-Mimicking Sulfono-γ-AApeptide Inhibitors for p53–MDM2/MDMX Protein–Protein Interactions Open
ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionNEXTORIGINAL ARTICLEThis notice is a correctionCorrection to α-Helix-Mimicking Sulfono-γ-AApeptide Inhibitors for p53–MDM2/MDMX Protein–Protein InteractionsPeng SangPeng SangMore by Peng …
View article: Rational Design and Synthesis of Right-Handed <scp>d</scp>-Sulfono-γ-AApeptide Helical Foldamers as Potent Inhibitors of Protein–Protein Interactions
Rational Design and Synthesis of Right-Handed <span>d</span>-Sulfono-γ-AApeptide Helical Foldamers as Potent Inhibitors of Protein–Protein Interactions Open
Novel unprecedented helical foldamers have been effectively designed and synthesized. The homogeneous right-handed d-sulfono-γ-AApeptides represent a new generation of unnatural helical peptidomimetics, which have similar folding conformat…
View article: α-Helix-Mimicking Sulfono-γ-AApeptide Inhibitors for p53–MDM2/MDMX Protein–Protein Interactions
α-Helix-Mimicking Sulfono-γ-AApeptide Inhibitors for p53–MDM2/MDMX Protein–Protein Interactions Open
The use of peptidomimetic scaffolds is a promising strategy for the inhibition of protein-protein interactions (PPIs). Herein, we demonstrate that sulfono-γ-AApeptides can be rationally designed to mimic the p53 α-helix and inhibit p53-MDM…
View article: Interaction between p53 N terminus and core domain regulates specific and nonspecific DNA binding
Interaction between p53 N terminus and core domain regulates specific and nonspecific DNA binding Open
Significance The p53 tumor suppressor is a sequence-specific DNA binding protein that activates gene transcription to regulate cell survival and proliferation. This report investigates the role of the p53 N-terminal transactivation domain …
View article: p53 Phosphomimetics Preserve Transient Secondary Structure but Reduce Binding to Mdm2 and MdmX
p53 Phosphomimetics Preserve Transient Secondary Structure but Reduce Binding to Mdm2 and MdmX Open
The disordered p53 transactivation domain (p53TAD) contains specific levels of transient helical secondary structure that are necessary for its binding to the negative regulators, mouse double minute 2 (Mdm2) and MdmX. The interactions of …
View article: Conserved Glycines Control Disorder and Function in the Cold-Regulated Protein, COR15A
Conserved Glycines Control Disorder and Function in the Cold-Regulated Protein, COR15A Open
Cold-regulated (COR) 15A is an intrinsically disordered protein (IDP) from Arabidopsis thaliana important for freezing tolerance. During freezing-induced cellular dehydration, COR15A transitions from a disordered to mostly α-helical struct…
View article: Conserved Helix-Flanking Prolines Modulate Intrinsically Disordered Protein:Target Affinity by Altering the Lifetime of the Bound Complex
Conserved Helix-Flanking Prolines Modulate Intrinsically Disordered Protein:Target Affinity by Altering the Lifetime of the Bound Complex Open
Appropriate integration of cellular signals requires a delicate balance of ligand-target binding affinities. Increasing the level of residual structure in intrinsically disordered proteins (IDPs), which are overrepresented in these cellula…
View article: Secondary interaction between MDMX and p53 core domain inhibits p53 DNA binding
Secondary interaction between MDMX and p53 core domain inhibits p53 DNA binding Open
Significance MDMX is a critical regulator of p53 and a potential drug target. The mechanisms by which MDMX inhibit p53 are not fully understood. Results in this report suggest that MDMX inhibits p53 DNA-binding function. Using a protein fr…