scholarly journals Structural Basis for α‐Helix Mimicry and Inhibition of Protein–Protein Interactions with Oligourea Foldamers

2020 ◽  
Author(s):  
Léonie Cussol ◽  
Laura Mauran‐Ambrosino ◽  
Jérémie Buratto ◽  
Anna Y Belorusova ◽  
Maxime Neuville ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Structural Basis ◽  
Protein Protein Interactions ◽  
Α Helix

scholarly journals Structural Basis for α‐Helix Mimicry and Inhibition of Protein–Protein Interactions with Oligourea Foldamers

2020 ◽  
Author(s):  
Léonie Cussol ◽  
Laura Mauran‐Ambrosino ◽  
Jérémie Buratto ◽  
Anna Y Belorusova ◽  
Maxime Neuville ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Structural Basis ◽  
Protein Protein Interactions ◽  
Α Helix

scholarly journals Peptide-based inhibitors of protein–protein interactions: biophysical, structural and cellular consequences of introducing a constraint

2021 ◽  
Author(s):  
Hongshuang Wang ◽  
Robert S. Dawber ◽  
Peiyu Zhang ◽  
Martin Walko ◽  
Andrew J. Wilson ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Α Helix ◽  
Cellular Behaviour

This review summarizes the influence of inserting constraints on biophysical, conformational, structural and cellular behaviour for peptides targeting α-helix mediated protein–protein interactions.

scholarly journals Interactions between Integrase and Excisionase in the Phage Lambda Excisive Nucleoprotein Complex

2002 ◽  
Vol 184 (18) ◽  
pp. 5200-5203 ◽  
Author(s):  
Eun Hee Cho ◽  
Richard I. Gumport ◽  
Jeffrey F. Gardner
Keyword(s):  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Mobility Shift ◽  
Host Chromosome ◽  
Amino Terminal ◽  
Nucleoprotein Complex ◽  
Carboxyl Terminal ◽  
Α Helix ◽  
Gel Mobility Shift ◽  
Amino Terminal Domain

ABSTRACT Bacteriophage lambda site-specific recombination comprises two overall reactions, integration into and excision from the host chromosome. Lambda integrase (Int) carries out both reactions. During excision, excisionase (Xis) helps Int to bind DNA and introduces a bend in the DNA that facilitates formation of the proper excisive nucleoprotein complex. The carboxyl-terminal α-helix of Xis is thought to interact with Int through direct protein-protein interactions. In this study, we used gel mobility shift assays to show that the amino-terminal domain of Int maintained cooperative interactions with Xis. This finding indicates that the amino-terminal arm-type DNA binding domain of Int interacts with Xis.

scholarly journals Optimal Anchoring of a Urea-based Foldamer Inhibitor of ASF1 Histone Chaperone Through Backbone Plasticity

2020 ◽  
Author(s):  
Johanne Mbianda ◽  
May Bakail ◽  
Christophe André ◽  
Gwenaëlle Moal ◽  
Marie E. Perrin ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Histone Chaperone ◽  
Protein Protein Interactions ◽  
Protein Surface ◽  
Chromatin Dynamics ◽  
Correct Orientation ◽  
Surface Recognition ◽  
Binding Interface ◽  
Helical Peptide ◽  
Α Helix

<p><b>Sequence-specific oligomers with predictable folding patterns, i.e. foldamers provide new opportunities to mimic α-helical peptides and design inhibitors of protein-protein interactions. One major hurdle of this strategy is to retain the correct orientation of key side chains involved in protein surface recognition. Here, we show that the structural plasticity of a foldamer backbone may significantly contribute to the required spatial adjustment for optimal interaction with the protein surface. By using oligoureas as α-helix mimics, we designed a foldamer/peptide hybrid inhibitor of histone chaperone ASF1, a key regulator of chromatin dynamics. The crystal structure of its complex with ASF1 reveals a striking plasticity of the urea backbone, which adapts to the ASF1 surface to maintain the same binding interface. One additional benefit of generating ASF1 ligands with non-peptide oligourea segments is the resistance to proteolysis in human plasma which was highly improved compared to the cognate α-helical peptide. </b></p>

scholarly journals Correction to α-Helix-Mimicking Sulfono-γ-AApeptide Inhibitors for p53–MDM2/MDMX Protein–Protein Interactions

2020 ◽  
Vol 63 (17) ◽  
pp. 10087-10087
Author(s):  
Peng Sang ◽  
Yan Shi ◽  
Junhao Lu ◽  
Lihong Chen ◽  
Leixiang Yang ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Α Helix

scholarly journals Keap1 Recruits Neh2 through Binding to ETGE and DLG Motifs: Characterization of the Two-Site Molecular Recognition Model

2006 ◽  
Vol 26 (8) ◽  
pp. 2887-2900 ◽  
Author(s):  
Kit I. Tong ◽  
Yasutake Katoh ◽  
Hideki Kusunoki ◽  
Ken Itoh ◽  
Toshiyuki Tanaka ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Isothermal Calorimetry ◽  
Biologically Active ◽  
Detoxification Enzymes ◽  
Bottom Surface ◽  
Transcriptional Level ◽  
Protein Protein Interactions ◽  
Intrinsically Disordered ◽  
Antioxidant Proteins ◽  
Α Helix

ABSTRACT The expression of the phase 2 detoxification enzymes and antioxidant proteins is induced at the transcriptional level by Nrf2 and negatively regulated at the posttranslational level by Keap1 through protein-protein interactions with and subsequent proteolysis of Nrf2. We found that the Neh2 domain of Nrf2 is an intrinsically disordered but biologically active regulatory domain containing a 33-residue central α-helix followed by a mini antiparallel β-sheet. Isothermal calorimetry analysis indicated that one Neh2 molecule interacts with two molecules of Keap1 via two binding sites, the stronger binding ETGE motif and the weaker binding DLG motif. Nuclear magnetic resonance titration study showed that these two motifs of the Neh2 domain bind to an overlapping site on the bottom surface of the β-propeller structure of Keap1. In contrast, the central α-helix of the Neh2 domain does not have any observable affinity to Keap1, suggesting that this region may serve as a bridge connecting the two motifs for the association with the two β-propeller structures of a dimer of Keap1. Based on these observations, we propose that Keap1 recruits Nrf2 by the ETGE motif and that the DLG motif of the Neh2 domain locks its lysine-rich central α-helix in a correct position to benefit ubiquitin signaling.

Uracil recognition by archaeal family B DNA polymerases

2003 ◽  
Vol 31 (3) ◽  
pp. 699-702 ◽  
Author(s):  
B.A. Connolly ◽  
M.J. Fogg ◽  
G. Shuttleworth ◽  
B.T. Wilson
Keyword(s):  
Dna Synthesis ◽  
Protein Interactions ◽  
Replication Fork ◽  
Dna Polymerases ◽  
Structural Basis ◽  
Dna Glycosylases ◽  
Protein Protein Interactions ◽  
Sensing Mechanism ◽  
Uridine Triphosphate

Archaeal family-B DNA polymerases possess a novel uracil-sensing mechanism. A specialized pocket scans the template, ahead of the replication fork, for the presence of uracil; on encountering this base, DNA synthesis is stalled. The structural basis for uracil recognition by polymerases is described and compared with other uracil-recognizing enzymes (uridine-triphosphate pyrophophatases and uracil-DNA glycosylases). Remarkably, protein–protein interactions between all three archaeal uracil sensors are observed; possibly the enzymes co-operate to efficiently eliminate uracil from archaeal genomes.

Sign in / Sign up

Export Citation Format

Share Document