SU(2) Cosmological Solitons

We present a class of numerical solutions to the SU(2) nonlinear $\sigma$-model coupled to the Einstein equations with cosmological constant $\Lambda\geq 0$ in spherical symmetry. These solutions are characterized by the presence of a regular static region which includes a center of symmetry. They are parameterized by a dimensionless ``coupling constant'' $\beta$, the sign of the cosmological constant, and an integer ``excitation number'' $n$. The phenomenology we find is compared to the corresponding solutions found for the Einstein-Yang-Mills (EYM) equations with positive $\Lambda$ (EYM$\Lambda$). If we choose $\Lambda$ positive and fix $n$, we find a family of static spacetimes with a Killing horizon for $0 \leq \beta < \beta_{max}$. As a limiting solution for $\beta = \beta_{max}$ we find a {\em globally} static spacetime with $\Lambda=0$, the lowest excitation being the Einstein static universe. To interpret the physical significance of the Killing horizon in the cosmological context, we apply the concept of a trapping horizon as formulated by Hayward. For small values of $\beta$ an asymptotically de Sitter dynamic region contains the static region within a Killing horizon of cosmological type. For strong coupling the static region contains an ``eternal cosmological black hole''.Comment: 20 pages, 6 figures, Revte

Molecular Mechanism of Thymidylate Synthase Inhibition by N 4 Hydroxy dCMP in View of Spectrophotometric and Crystallographic Studies

Novel evidence is presented allowing further clarification of the mechanism of the slow binding thymidylate synthase TS inhibition by N4 hydroxy dCMP N4 OH dCMP . Spectrophotometric monitoring documented time and temperature , and N4 OH dCMP dependent TS catalyzed dihydrofolate production, accompanying the mouse enzyme incubation with N4 OH dCMP and N5,10 methylenetetrahydrofolate, known to inactivate the enzyme by the covalent binding of the inhibitor, suggesting the demonstrated reaction to be uncoupled from the pyrimidine C 5 methylation. The latter was in accord with the hypothesis based on the previously presented structure of mouse TS cf. PDB ID 4EZ8 , and with conclusions based on the present structure of the parasitic nematode Trichinella spiralis, both co crystallized with N4 OH dCMP and N5,10 methylenetetrahdrofolate. The crystal structure of the mouse TS N4 OH dCMP complex soaked with N5,10 methylenetetrahydrofolate revealed the reaction to run via a unique imidazolidine ring opening, leaving the one carbon group bound to the N 10 atom, thus too distant from the pyrimidine C 5 atom to enable the electrophilic attack and methylene group transfe

Two-Dimensional Infrared Spectroscopy of Antiparallel β-Sheet Secondary Structure

We investigate the sensitivity of femtosecond Fourier transform two-dimensional infrared spectroscopy to protein secondary structure with a study of antiparallel β-sheets. The results show that 2D IR spectroscopy is more sensitive to structural differences between proteins than traditional infrared spectroscopy, providing an observable that allows comparison to quantitative models of protein vibrational spectroscopy. 2D IR correlation spectra of the amide I region of poly-L-lysine, concanavalin A, ribonuclease A, and lysozyme show cross-peaks between the IR-active transitions that are characteristic of amide I couplings for polypeptides in antiparallel hydrogen-bonding registry. For poly-L-lysine, the 2D IR spectrum contains the eight-peak structure expected for two dominant vibrations of an extended, ordered antiparallel β-sheet. In the proteins with antiparallel β-sheets, interference effects between the diagonal and cross-peaks arising from the sheets, combined with diagonally elongated resonances from additional amide transitions, lead to a characteristic “Z”-shaped pattern for the amide I region in the 2D IR spectrum. We discuss in detail how the number of strands in the sheet, the local configurational disorder in the sheet, the delocalization of the vibrational excitation, and the angle between transition dipole moments affect the position, splitting, amplitude, and line shape of the cross-peaks and diagonal peaks.

Structure and pathogenesis of disorders releated to CNG repeat

CNG repeats (N stands for one of the four natural nucleotides) are a special class of microsatellite sequences of the human genome. They are most often found in exons, in their coding parts as well as in the 5’ or 3’ untranslated regions. Characteristic frequencies of their occurrence within the different parts of the genes suggest that they play a functional role. The number of CNG repeats in a block is usually below 30 but it can undergo abnormal expansion leading to the development of one of approximately 20 neurological diseases known as TREDs (Triplet Repeat Expansion Disorders). One model of pathogenesis proposes that the toxic factor is mRNA containing an expanded run of CNG repeats. The anomaly results in aberrant alternative splicing and/or accumulation of the RNA in the cell nucleus, followed by a sequestration of important regulatory proteins and formation of RNA/ protein aggregates known as nuclear foci. This is accompanied by a deregulation of vital cellular processes. In this paper we have focused on crystallographic studies of RNA oligomers with embedded CNG repeats. We describe briefly diseases associated with each type of repeat and present the crystal structures. All the CNG repeats form stable “hairpins” consisting of a small apical loop and a long double-stranded stem, in which the non-canonical N-N pairs are flanked by the standard C-G and G-C pairs. All CNG repeats form duplexes of type A, characteristic of RNA, but with local deviations from the typical geometry (Fig. 1). The duplexes are stabilised by the strong C-G and G-C Watson-Crick interactions, while the N-N pairs are accommodated within the helical context, each in a characteristic way (Fig. 2). The U-U pairs tend to form just one hydrogen bond, instead of two observed in other contexts. The interactions within the C-C pairs are even weaker, via one very weak hydrogen bond or none. On the other hand, accommodation of the bulky A-A pairs involves pushing the purine rings towards the major groove while in the G-G pairs one of the guanosine residues flips to a syn conformation. The unrealised hydrogen-bonding potential of the N-N pairs is externalised into the major and the minor grooves and can be assessed through interactions with ordered water molecules and other small ligands. The N-N pairs are associated with local distortions of the A-helix (Fig. 1). All the CNG repeats show a characteristic striped pattern of surface electrostatic potential in the minor groove (Fig. 3). Assessment of the different CNG structures allows us to identify the characteristic and the common features (Tab. 1)

The crystal structure of a streptomyces thermoviolaceus thermophilic chitinase known for its refolding efficiency

Analyzing the structure of proteins from extremophiles is a promising way to study the rules governing the protein structure, because such proteins are results of structural and functional optimization under well-defined conditions. Studying the structure of chitinases addresses an interesting aspect of enzymology, because chitin, while being the world’s second most abundant biopolymer, is also a recalcitrant substrate. The crystal structure of a thermostable chitinase from Streptomyces thermoviolaceus (StChi40) has been solved revealing a β/α-barrel (TIM-barrel) fold with an α+β insertion domain. This is the first chitinase structure of the multi-chitinase system of S. thermoviolaceus. The protein is also known to refold efficiently after thermal or chemical denaturation. StChi40 is structurally close to the catalytic domain of psychrophilic chitinase B from Arthrobacter TAD20. Differences are noted in comparison to the previously examined chitinases, particularly in the substrate-binding cleft. A comparison of the thermophilic enzyme with its psychrophilic homologue revealed structural features that could be attributed to StChi40’s thermal stability: Compactness of the structure with trimmed surface loops and unique disulfide bridges, one of which is additionally stabilized by S–π interactions with aromatic rings. Uncharacteristically for thermophilic proteins, StChi40 has fewer salt bridges than its mesophilic and psychrophilic homologues. © 2020 by the authors. Licensee MDPI, Basel, Switzerland