Disruption of NBS1/MRN Complex Formation by E4orf3 Supports NF-κB That Licenses E1B55K-Deleted Adenovirus-Infected Cells to Accumulate DNA>4n

Genome instability, a hallmark of cancer, exists as part of a cycle that leads to DNA damage and DNA > 4n that further enhances genome instability. Ad E4orf3 is a viral oncogene. Here, we describe E4orf3 mediated signaling events that support DNA > 4n in Δ E1B Ad-infected cells. These signaling events may be linked to the oncogenic potential of E4orf3 and may provide a basis for how some cells survive with DNA > 4n.

MD Simulation of AEDG Peptide Complexes with New K2R Dendrimer and Dendrigraft

Biocompatible peptide dendrimers and dendrigrafts have useful properties for application in biomedicine. In previous papers the computational approach for study lysine dendrimers and dendrigrafts as well as their complexes with various medical peptides was used. In this paper the comparison of complex formation between molecules of therapeutic AEDG tetrapeptide and novel K2R peptide dendrimer or DG2 dendrigraft of near the same size and charge was fulfilled. The systems consisting of 16 therapeutic AEDG tetrapeptide molecules and one dendrimer or one dendrigraft were studied by molecular dynamics simulation. Full atomic models of these molecules in water with explicit counterions were used for this goal. First of all, the process of complex formation was studied. It was obtained that peptide molecules were attracted by both branched molecules and were quickly adsorbed by them. Times of complexes formation as well as size, anisotropy and structure of each complex were calculated. It was demonstrated that both K2R dendrimer and DG2 dendrigraft are effective for complexation of these peptide molecules but new dendrimer complex is more stable than dendrigraft complex because it has almost twice more hydrogen bonds with peptide molecules and 33% more ion pairs with their charged groups.

Orchestrating serine/threonine phosphorylation and elucidating downstream effects by short linear motifs

Cellular function is based on protein–protein interactions. A large proportion of these interactions involves the binding of short linear motifs (SLiMs) by folded globular domains. These interactions are regulated by post-translational modifications, such as phosphorylation, that create and break motif binding sites or tune the affinity of the interactions. In addition, motif-based interactions are involved in targeting serine/threonine kinases and phosphatases to their substrate and contribute to the specificity of the enzymatic actions regulating which sites are phosphorylated. Here, we review how SLiM-based interactions assist in determining the specificity of serine/threonine kinases and phosphatases, and how phosphorylation, in turn, affects motif-based interactions. We provide examples of SLiM-based interactions that are turned on/off, or are tuned by serine/threonine phosphorylation and exemplify how this affects SLiM-based protein complex formation.

Effect of Trastuzumab–HER2 Complex Formation on Stress-Induced Modifications in the CDRs of Trastuzumab

Asparagine deamidation and aspartic acid isomerization in the complementarity determining regions (CDRs) of monoclonal antibodies may alter their affinity to the target antigen. Trastuzumab has two hot spots for deamidation and one position for isomerization in the CDRs. Little is known how complex formation with its target antigen HER2 affects these modifications. Modifications in the CDRs of trastuzumab were thus compared between the free antibody and the trastuzumab–HER2 complex when stressed under physiological conditions at 37°C. Complex formation and stability of the complex upon stressing were assessed by size-exclusion chromatography. Deamidation of light-chain Asn-30 (Lc-Asn-30) was extensive when trastuzumab was stressed free but reduced about 10-fold when the antibody was stressed in complex with HER2. Almost no deamidation of heavy-chain (Hc-Asn-55) was detected in the trastuzumab–HER2 complex, while deamidation was observed when the antibody was stressed alone. Hc-Asp-102 isomerization, a modification that critically affects biological activity, was observed to a moderate degree when the free antibody was stressed but was not detected at all in the trastuzumab–HER2 complex. This shows that complex formation has a major influence on critical modifications in the CDRs of trastuzumab.

Optical Absorption, Kinetics and Thermodynamic Studies of Pr(III) and Nd(III) Ions with N-Acetyl L-Cysteine in Presence of Ca(II) ions

Interaction of N-acetyl-L-cysteine (NAC) with Pr3+ (Pr(NO3)3·6H2O) and Nd3+ (Nd(NO3)3·6H2O) ions are studied in presence of Ca2+ (Ca(NO3)3·4H2O) ion in an aqueous and organic solvent by applying the spectroscopic technique for quantitative probe of 4f-4f transition. The complexation was determined by the variation in the intensities of 4f-4f absorption spectral bands and by applying the change of symmetric properties of electronic-dipole known as Judd-Ofelt parameters Tλ (λ = 2,4,6). On the addition of Ca2+ ion in the binary complexation of praseodymium and neodymium with N-acetyl-L-cysteine (NAC) there is an intensification of bands which shows the effect of Ca2+ toward the heterobimetallic complex formation. Other parameters like Slater-Condon (Fk), bonding (b1/2), the Nephelauxetic ratio (β), percentage covalency (δ) are also used to correlate the complexation of metals with N-acetyl-L-cysteine (NAC). With the minor change in coordination around Pr3+ and Nd3+ ions, the sensitivity of 4f-4f bands is detected and further used to explain the coordination of N-acetyl-L-cysteine (NAC) with Pr3+ and Nd3+ in presence of Ca2+. The variation in oscillator strength (Pobs), energy (Eobs) and dipole intensity parameter help in supporting the heterobimetallic complexation of N-acetyl-L-cysteine. In kinetics investigation, the rate of the complexation of both hypersensitive and pseudo-hypersensitive transition is evaluated at various temperature in DMF solvent. The value of the thermodynamic parameters such as ΔHo, ΔSo and ΔGo and activation energy (Ea) also evaluated.

Macro-B12 masking B12 deficiency

In clinical practice, the finding of an elevated serum B12 concentration is often the consequence of supplementation with B12 in either oral form or injections. Also, elevated serum B12 may be associated with underlying disorders, like liver diseases or a (haematologic) malignancy. Only a few studies have shown that it may also be the consequence of complex formation of B12-vitamin binding proteins with immunoglobulins, the so-called macro-B12. We describe a young woman who previously was diagnosed with B12 deficiency, and in whom, after cessation of B12 injection treatment, neurologic symptoms re-appeared, and despite this, repeatedly elevated serum B12 concentrations above the upper limit of the assay were found. We demonstrated that this was caused by the presence of macro-B12, which not only resulted in erroneous and longstanding elevated serum B12, but also masked her underlying B12 deficiency.

Peptide cyclisation promoted by supramolecular complex formation

Phenol ester activated dipeptides that are reluctant to ring-closure have been cyclised with the aid of sterically shielding metallo-porphyrins avoiding unwanted intermolecular reactions. The binding of ZnTPP to the dipyridine-functionalised...

Light-Up Carbon Dots for Copper (II) Detection by Aggregation-Induced Enhanced Strategy

Carbon dots have promising prospects for analytical and monitoring purposes but are greatly hindered by the aggregation-induced luminescence quenching owing to the π-π interaction or the non-radiation-excited radical complex formation....