Exceptional stability of the sugammadex-solasodine complex: Insights from experimental and theoretical studies.

Sugammadex (SGM) is the first cyclodextrin (CD)-based selective relaxant binding agent. We investigated its ability to capture natural aminosteroid phytotoxins, and assessed its potential as an antidote for intoxication. Solasodine (SS), a toxic alkaloid from the Solanaceae family, was chosen as the model compound.

Assignment of the disordered, proline-rich N-terminal domain of the tumour suppressor p53 protein using H and H-detected NMR measurements.

Protein p53 is mostly known for playing a key role in tumour suppression, and mutations in the p53 gene are amongst the most frequent genomic events accompanying oncogenic transformation. Continuous research is conducted to target disordered proteins/protein regions for cancer therapy, for which atomic level information is also necessary. The disordered N-terminal part of p53 contains the transactivation and the proline-rich domains-which besides being abundant in proline residues-contains repetitive Pro-Ala motifs.

Proline Isomerization in Intrinsically Disordered Proteins and Peptides.

Background: Intrinsically disordered proteins and protein regions (IDPs/IDRs) are important in diverse biological processes. Lacking a stable secondary structure, they display an ensemble of conformations. One factor contributing to this conformational heterogeneity is the proline isomerization.

The Disordered EZH2 Loop: Atomic Level Characterization by H- and H-Detected NMR Approaches, Interaction with the Long Noncoding HOTAIR RNA.

The 96-residue-long loop of EZH2 is proposed to play a role in the interaction with long non-coding RNAs (lncRNAs) and to contribute to EZH2 recruitment to the chromatin. However, molecular details of RNA recognition have not been described so far. Cellular studies have suggested that phosphorylation of the Thr345 residue localized in this loop influences RNA binding; however, no mechanistic explanation has been offered.

Monitoring Protein Global and Local Parameters in Unfolding and Binding Studies: The Extended Applicability of the Diffusion Coefficient─Molecular Size Empirical Relations.

Protein unfolding and denaturation are main issues in biochemical and pharmaceutical research. Using a global parameter, the translational diffusion coefficient , folded, unfolded, and intrinsically disordered proteins of a given molar mass can be distinguished based on their distinct hydrodynamic properties. For broader applications, we provide generalized, PFG-NMR-based empirical relations validated at different temperatures and ready to use with the corresponding corrections in different media.

Novel Lysine-Rich Delivery Peptides of Plant Origin ERD and Human S100: The Effect of Carboxyfluorescein Conjugation, Influence of Aromatic and Proline Residues, Cellular Internalization, and Penetration Ability.

The need for novel drug delivery peptides is an important issue of the modern pharmaceutical research. Here, we test K-rich peptides from plant dehydrin ERD14 (ERD-A, ERD-B, and ERD-C) and the C-terminal CPP-resembling region of S100A4 (S100) using the 5(6)-carboxyfluorescein (Cf) tag at the N-terminus. Via a combined pH-dependent NMR and fluorescence study, we analyze the effect of the Cf conjugation/modification on the structural behavior, separately investigating the (5)-Cf and (6)-Cf forms.

Selective H NMR Methods Reveal Functionally Relevant Proline cis/trans Isomers in Intrinsically Disordered Proteins: Characterization of Minor Forms, Effects of Phosphorylation, and Occurrence in Proteome.

It is important to identify proline cis/trans isomers that appear in several regulatory mechanisms of proteins, and to characterize minor species that are present due to the conformational heterogeneity in intrinsically disordered proteins (IDPs). To obtain residue level information on these mobile systems we introduce two H -detected, proline selective, real-time homodecoupled NMR experiments and analyze the proline abundant transactivation domain of p53. The measurements are sensitive enough to identify minor conformers present in 4-15 % amounts; moreover, we show the consequences of CK2 phosphorylation on the cis/trans-proline equilibrium.

Tumor-Suppressor p53TAD Forms a Fuzzy Complex with Metastasis-Associated S100A4: Structural Insights and Dynamics by an NMR/MD Approach.

Conformationally flexible protein complexes represent a major challenge for structural and dynamical studies. We present herein a method based on a hybrid NMR/MD approach to characterize the complex formed between the disordered p53TAD and the metastasis-associated S100A4. Disorder-to-order transitions of both TAD1 and TAD2 subdomains upon interaction is detected.

Anionic food color tartrazine enhances antibacterial efficacy of histatin-derived peptide DHVAR4 by fine-tuning its membrane activity.

Here it is demonstrated how some anionic food additives commonly used in our diet, such as tartrazine (TZ), bind to DHVAR4, an antimicrobial peptide (AMP) derived from oral host defense peptides, resulting in significantly fostered toxic activity against both Gram-positive and Gram-negative bacteria, but not against mammalian cells. Biophysical studies on the DHVAR4-TZ interaction indicate that initially large, positively charged aggregates are formed, but in the presence of lipid bilayers, they rather associate with the membrane surface. In contrast to synergistic effects observed for mixed antibacterial compounds, this is a principally different mechanism, where TZ directly acts on the membrane-associated AMP promoting its biologically active helical conformation.

Directed Evolution of Canonical Loops and Their Swapping between Unrelated Serine Proteinase Inhibitors Disprove the Interscaffolding Additivity Model.

Reversible serine proteinase inhibitors comprise 18 unrelated families. Each family has a distinct representative structure but contains a surface loop that adopts the same, canonical conformation in the enzyme-inhibitor complex. The Laskowski mechanism universally applies for the action of all canonical inhibitors independent of their scaffold, but it has two nontrivial extrapolations.