Insights into stabilizing interactions in the distorted domain-swapped dimer of Salmonella typhimurium survival protein

The survival protein SurE from Salmonella typhimurium (StSurE) is a dimeric protein that functions as a phosphatase. SurE dimers are formed by the swapping of a loop with a pair of beta-strands and a C-terminal helix between two protomers. In a previous study, the Asp230 and His234 residues were mutated to Ala to abolish a hydrogen bond that was thought to be crucial for C-terminal helix swapping. These mutations led to functionally inactive and distorted dimers in which the two protomers were related by a rotation of 167 degrees. New salt bridges involving Glu112 were observed in the dimeric interface of the H234A and D230A/H234A mutants. To explore the role of these salt bridges in the stability of the distorted structure, E112A, E112A/D230A, E112A/H234A, E112A/D230A/H234A, R179L/H180A/H234A and E112A/R179L/H180A/H234A mutants were constructed. X-ray crystal structures of the E112A, E112A/H234A and E112A/D230A mutants could be determined. The dimeric structures of the E112A and E112A/H234A mutants were similar to that of native SurE, while the E112A/D230A mutant had a residual rotation of 11 degrees between the B chains upon superposition of the A chains of the mutant and native dimers. The native dimeric structure was nearly restored in the E112A/H234A mutant, suggesting that the new salt bridge observed in the H234A and D230A/H234A mutants was indeed responsible for the stability of their distorted structures. Catalytic activity was also restored in these mutants, implying that appropriate dimeric organization is necessary for the activity of SurE.

S center dot center dot center dot O chalcogen bonding in sulfa drugs: insights from multipole charge density and X-ray wavefunction of acetazolamide

Experimental charge density analysis combined with the quantum crystallographic technique of X-ray wavefunction refinement (XWR) provides quantitative insights into the intra-and intermolecular interactions formed by acetazolamide, a diuretic drug. Firstly, the analysis of charge density topology at the intermolecular level shows the presence of exceptionally strong interaction motifs such as a DDAA-AADD (D-donor, A-acceptor) type quadruple hydrogen bond motif and a sulfonamide dimer synthon. The nature and strength of intra-molecular S center dot center dot center dot O chalcogen bonding have been characterized using descriptors from the multipole model (MM) and XWR. Although pure geometrical criteria suggest the possibility of two intra-molecular S center dot center dot center dot O chalcogen bonded ring motifs, only one of them satisfies the ``orbital geometry'' so as to exhibit an interaction in terms of an electron density bond path and a bond critical point. The presence of `s-holes' on the sulfur atom leading to the S center dot center dot center dot O chalcogen bond has been visualized on the electrostatic potential surface and Laplacian isosurfaces close to the `reactive surface'. The electron localizability indicator (ELI) and Roby bond orders derived from the `experimental wave function' provide insights into the nature of S center dot center dot center dot O chalcogen bonding.

New physical insights into the electromagnetic shielding efficiency in PVDF nanocomposites containing multiwall carbon nanotubes and magnetic nanoparticles

This work attempts to bring critical insights into the electromagnetic shielding efficiency in polymeric nanocomposites with respect to the particle size of magnetic nanoparticles added along with or without a conductive inclusion. To gain insight, various Ni-Fe (NixFe1-x; x = 10, 20, 40; Ni: nickel, Fe: iron) alloys were prepared by a vacuum arc melting process and different particle sizes were then achieved by a controlled grinding process for different time scales. Poly(vinylidene fluoride), PVDF based composites involving different particle sizes of the Ni-Fe alloy were prepared with or without multiwall carbon nanotubes (MWNTs) by a wet grinding approach. The Ni-Fe particles were thoroughly characterized with respect to their microstructure and magnetization; and the electromagnetic (EM) shielding efficiency (SE) of the resulting composites was obtained from the scattering parameters using a vector network analyzer in a broad range of frequencies. The saturation magnetization of Ni-Fe nanoparticles and the bulk electrical conductivity of PVDF/Ni-Fe composites scaled with increasing particle size of NiFe. Interestingly, the PVDF/Ni-Fe/MWNT composites showed a different trend where the bulk electrical conductivity and SE scaled with decreasing particle size of the Ni-Fe alloy. A total SE of similar to 35 dB was achieved with 50 wt% of Ni60Fe40 and 3 wt% MWNTs. More interestingly, the PVDF/Ni-Fe composites shielded the EM waves mostly by reflection whereas, the PVDF/Ni-Fe/MWNT shielded mostly by absorption. A minimum reflection loss of similar to 58 dB was achieved in the PVDF/Ni-Fe/MWNT composites in the X-band (8-12 GHz) for a particular size of Ni-Fe alloy nanoparticles. This study brings new insights into the EM shielding efficiency in PVDF/magnetic nanoparticle based composites in the presence and absence of conducting inclusion.

Structural insights into N-terminal to C-terminal interactions and implications for thermostability of a (beta/alpha)(8)-triosephosphate isomerase barrel enzyme

Although several factors have been suggested to contribute to thermostability, the stabilization strategies used by proteins are still enigmatic. Studies on a recombinant xylanase from Bacilllus sp. NG-27 (RBSX), which has the ubiquitous (beta/alpha)(8)-triosephosphate isomerase barrel fold, showed that just a single mutation, V1L, although not located in any secondary structural element, markedly enhanced the stability from 70 degrees C to 75 degrees C without loss of catalytic activity. Conversely, the V1A mutation at the same position decreased the stability of the enzyme from 70 degrees C to 68 degrees C. To gain structural insights into how a single extreme N-terminus mutation can markedly influence the thermostability of the enzyme, we determined the crystal structure of RBSX and the two mutants. On the basis of computational analysis of their crystal structures, including residue interaction networks, we established a link between N-terminal to C-terminal contacts and RBSX thermostability. Our study reveals that augmenting N-terminal to C-terminal noncovalent interactions is associated with enhancement of the stability of the enzyme. In addition, we discuss several lines of evidence supporting a connection between N-terminal to C-terminal noncovalent interactions and protein stability in different proteins. We propose that the strategy of mutations at the termini could be exploited with a view to modulate stability without compromising enzymatic activity, or in general, protein function in diverse folds where N and C termini are in close proximity. Database The coordinates of RBSX, V1A and V1L have been deposited in the PDB database under the accession numbers 4QCE, 4QCF, and 4QDM, respectively

Insights into the catalytic mechanism of synthetic glutathione peroxidase mimetics

Glutathione Peroxidase (GPx) is a key selenoenzyme that protects biomolecules from oxidative damage. Extensive research has been carried out to design and synthesize small organoselenium compounds as functional mimics of GPx. While the catalytic mechanism of the native enzyme itself is poorly understood, the synthetic mimics follow different catalytic pathways depending upon the structures and reactivities of various intermediates formed in the catalytic cycle. The steric as well as electronic environments around the selenium atom not only modulate the reactivity of these synthetic mimics towards peroxides and thiols, but also the catalytic mechanisms. The catalytic cycle of small GPx mimics is also dependent on the nature of peroxides and thiols used in the study. In this review, we discuss how the catalytic mechanism varies with the substituents attached to the selenium atom.

Notch sensitivity in nanoscale metallic glass specimens: Insights from continuum simulations

Recent experiments have shown that nano-sized metallic glass (MG) specimens subjected to tensile loading exhibit increased ductility and work hardening. Failure occurs by necking as opposed to shear banding which is seen in bulk samples. Also, the necking is generally observed at shallow notches present on the specimen surface. In this work, continuum finite element analysis of tensile loading of nano-sized notched MG specimens is conducted using a thermodynamically consistent non-local plasticity model to clearly understand the deformation behavior from a mechanics perspective. It is found that plastic zone size in front of the notch attains a saturation level at the stage when a dominant shear band forms extending across the specimen. This size scales with an intrinsic material length associated with the interaction stress between flow defects. A transition in deformation behavior from quasi-brittle to ductile becomes possible when this critical plastic zone size is larger than the uncracked ligament length. These observations corroborate with atomistic simulations and experimental results. (C) 2015 Elsevier Ltd. All rights reserved.

Part I: Physical Insights Into the Two-Stage Breakdown Characteristics of STI-Type Drain-Extended pMOS Device

In this paper, we study breakdown characteristics in shallow-trench isolation (STI)-type drain-extended MOSFETs (DeMOS) fabricated using a low-power 65-nm triple-well CMOS process with a thin gate oxide. Experimental data of p-type STI-DeMOS device showed distinct two-stage behavior in breakdown characteristics in both OFF-and ON-states, unlike the n-type device, causing a reduction in the breakdown voltage and safe operating area. The first-stage breakdown occurs due to punchthrough in the vertical structure formed by p-well, deep n-well, and p-substrate, whereas the second-stage breakdown occurs due to avalanche breakdown of lateral n-well/p-well junction. The breakdown characteristics are also compared with the STI-DeNMOS device structure. Using the experimental results and advanced TCAD simulations, a complete understanding of breakdown mechanisms is provided in this paper for STI-DeMOS devices in advanced CMOS processes.

Physical Insights on the Ambiguous Metal-Graphene Interface and Proposal for Improved Contact Resistance

The ambiguous behavior of metal-graphene interface has been addressed in this paper using density functional theory and nonequilibrium Green's function formalism. For the first time, the fundamental chemistry of metal-graphene interface, in particular role of sp-hybridized and sp(2)-hybridized carbon atoms, has been emphasized and discussed in detail in this paper. It was discovered that the sp-hybridized sites at the edge of a graphene monolayer contribute to 40% of current conduction when compared with sp(2)-hybridized atom sites in the graphene-metal overlap region. Moreover, we highlighted the insignificance of an additional metal layer, i.e., sandwiched contact, due to lacking sp-hybridized carbon sites. A fundamental way of defining the contact resistance, while keeping chemical bonding in mind, has been proposed. The bonding insight has been further used to propose the novel ways of interfacing metal with graphene, which results in a 40% reduction in contact resistance.

Rapid synthesis of hybrids and hollow PdO nanostructures by controlled in situ dissolution of a ZnO nanorod template: insights into the formation mechanism and thermal stability

Hollow nanomaterials have attracted a lot of interest by virtue of their wide range of applications that arise primarily due to their unique architecture. A common strategy to synthesize hollow nanomaterials is by nucleation of the shell material over a preformed core and subsequent dissolution of the core in the second step. Herein an ultrafast, microwave route has been demonstrated, to synthesize PdO nanotubes in a single step using ZnO as a sacrificial template. The mechanism of the nanotube formation has been investigated in detail using control experiments. By tuning the starting ratio of PdCl2 : ZnO, hollow to hybrid PdO nanostructures could be obtained using the same method. Conversion of the PdO to Pd nanotubes has been shown by simple NaBH4 treatment. The thermal stability of the PdO nanotubes has been studied. The insights presented here are general and applicable for the synthesis of hybrids/hollow structures in other systems as well.

Structural studies on tobacco streak virus coat protein: Insights into the pleomorphic nature of ilarviruses

Tobacco streak virus (TSV), the type member of Ilarvirus genus, is a major plant pathogen. TSV purified from infected plants consists of a ss-RNA genome encapsidated in spheroidal particles with diameters of 27, 30 and 33 nm constructed from multiple copies of a single species of coat protein (CP) subunits. Apart from protecting the viral genome, CPs of ilarviruses play several key roles in the life cycle of these viruses. Unlike the related bromo and cucumoviruses, ilarvirus particles are labile and pleomorphic, which has posed difficulties in their crystallization and structure determination. In the current study, a truncated TSV-CP was crystallized in two distinct forms and their structures were determined at resolutions of 2.4 angstrom and 2.1 angstrom, respectively. The core of TSV CP was found to possess the canonical beta-barrel jelly roll tertiary structure observed in several other viruses. Dimers of CP with swapped C-terminal arms (C-arm) were observed in both the crystal forms. The C-arm was found to be flexible and is likely to be responsible for the polymorphic and pleomorphic nature of TSV capsids. Consistent with this observation, mutations in the hinge region of the C-arm that reduce the flexibility resulted in the formation of more uniform particles. TSV CP was found to be structurally similar to that of Alfalfa mosaic virus (AMV) accounting for similar mechanism of genome activation in alfamo and ilar viruses. This communication represents the first report on the structure of the CP from an ilarvirus. (C) 2015 Elsevier Inc. All rights reserved.

Physical insights into salicylic acid release from poly(anhydrides)

Salicylic acid (SA) based biodegradable polyanhydrides (PAHs) are of great interest for drug delivery in a variety of diseases and disorders owing to the multi-utility of SA. There is a need for the design of SA-based PAHs for tunable drug release, optimized for the treatment of different diseases. In this study, we devised a simple strategy for tuning the release properties and erosion kinetics of a family of PAHs. PAHs incorporating SA were derived from related aliphatic diacids, varying only in the chain length, and prepared by simple melt condensation polymerization. Upon hydrolysis induced erosion, the polymer degrades into cytocompatible products, including the incorporated bioactive SA and diacid. The degradation follows first order kinetics with the rate constant varying by nearly 25 times between the PAH obtained with adipic acid and that with dodecanedioic acid. The release profiles have been tailored from 100% to 50% SA release in 7 days across the different PAHs. The release rate constants of these semi-crystalline, surface eroding PAHs decreased almost linearly with an increase in the diacid chain length, and varied by nearly 40 times between adipic acid and dodecanedioic acid PAH. The degradation products with SA concentration in the range of 30-350 ppm were used to assess cytocompatibility and showed no cytotoxicity to HeLa cells. This particular strategy is expected to (a) enable synthesis of application specific PAHs with tunable erosion and release profiles; (b) encompass a large number of drugs that may be incorporated into the PAH matrix. Such a strategy can potentially be extended to the controlled release of other drugs that may be incorporated into the PAH backbone and has important implications for the rational design of drug eluting bioactive polymers.

Ionothermal Synthesis of High-Voltage Alluaudite Na2+2xFe2-x(SO4)(3) Sodium Insertion Compound: Structural, Electronic, and Magnetic Insights

Exploring future cathode materials for sodium-ion batteries, alluaudite class of Na2Fe2II(SO4)(3) has been recently unveiled as a 3.8 V positive insertion candidate (Barpanda et al. Nat. Commun. 2014, 5, 4358). It forms an Fe-based polyanionic compound delivering the highest Fe-redox potential along with excellent rate kinetics and reversibility. However, like all known SO4-based insertion materials, its synthesis is cumbersome that warrants careful processing avoiding any aqueous exposure. Here, an alternate low temperature ionothermal synthesis has been described to produce the alluaudite Na2+2xFe2-xII(SO4)(3). It marks the first demonstration of solvothermal synthesis of alluaudite Na2+2xM2-xII(SO4)(3) (M = 3d metals) family of cathodes. Unlike classical solid-state route, this solvothermal route favors sustainable synthesis of homogeneous nanostructured alluaudite products at only 300 degrees C, the lowest temperature value until date. The current work reports the synthetic aspects of pristine and modified ionothermal synthesis of Na2+2xFe2-xII(SO4)(3) having tunable size (300 nm similar to 5 mu m) and morphology. It shows antiferromagnetic ordering below 12 K. A reversible capacity in excess of 80 mAh/g was obtained with good rate kinetics and cycling stability over 50 cycles. Using a synergistic approach combining experimental and ab initio DFT analysis, the structural, magnetic, electronic, and electrochemical properties and the structural limitation to extract full capacity have been described.

In Situ NMR Insights into the Electrochemical Reaction of Cu3P Electrodes in Lithium Batteries

This study reports a multinuclei in situ (real-time) NMR spectroscopic characterization of the electrochemical reactions of a negative Cu3P electrode toward lithium. Taking advantage of the different nuclear spin characteristics, we have obtained real-time P-31 and Li-7 NMR data for a comprehensive understanding of the electrochemical mechanism during the discharge and charge processes of a lithium battery. The large NMR chemical shift span of P-31 facilitates the observation of the chemical evolutions of different lithiated and delithiated LixCu3-xP phases, whereas the quadrupolar line features in Li-7 enable identification of asymmetric Li sites. These combined NMR data offer an unambiguous identification of four distinct LixCu3-xP phases, Cu3P, Li0.2Cu2.8P, Li2CuP, and. Li3P, and the characterization of their involvement in the electrochemical reactions. The NMR data led us to propose a delithiation process involving the intercalation of metallic Cu-0 atomic aggregates into the Li2CuP structure to form a Cu-0-Li2-xCu1-xP phase. This process might be responsible for the poor capacity retention in Cu3P lithium batteries when cycled to a low voltage.

Depletion of nonlinearity in magnetohydrodynamic turbulence: Insights from analysis and simulations

It is shown how suitably scaled, order-m moments, D-m(+/-), of the Elsasser vorticity fields in three-dimensional magnetohydrodynamics (MHD) can be used to identify three possible regimes for solutions of the MHD equations with magnetic Prandtl number P-M = 1. These vorticity fields are defined by omega(+/-) = curl z(+/-) = omega +/- j, where z(+/-) are Elsasser variables, and where omega and j are, respectively, the fluid vorticity and current density. This study follows recent developments in the study of three-dimensional Navier-Stokes fluid turbulence Gibbon et al., Nonlinearity 27, 2605 (2014)]. Our mathematical results are then compared with those from a variety of direct numerical simulations, which demonstrate that all solutions that have been investigated remain in only one of these regimes which has depleted nonlinearity. The exponents q(+/-) that characterize the inertial range power-law dependencies of the z(+/-) energy spectra, epsilon(+/-)(k), are then examined, and bounds are obtained. Comments are also made on (a) the generalization of our results to the case P-M not equal 1 and (b) the relation between D-m(+/-) and the order-m moments of gradients of magnetohydrodynamic fields, which are used to characterize intermittency in turbulent flows.

Connecting Active-Site Loop Conformations and Catalysis in Triosephosphate Isomerase: Insights from a Rare Variation at Residue96 in the Plasmodial Enzyme

Despite extensive research into triosephosphate isomerases (TIMs), there exists a gap in understanding of the remarkable conjunction between catalytic loop-6 (residues 166-176) movement and the conformational flip of Glu165 (catalytic base) upon substrate binding that primes the active site for efficient catalysis. The overwhelming occurrence of serine at position96 (98% of the 6277 unique TIM sequences), spatially proximal to E165 and the loop-6 residues, raises questions about its role in catalysis. Notably, Plasmodium falciparum TIM has an extremely rare residuephenylalanineat this position whereas, curiously, the mutant F96S was catalytically defective. We have obtained insights into the influence of residue96 on the loop-6 conformational flip and E165 positioning by combining kinetic and structural studies on the PfTIM F96 mutants F96Y, F96A, F96S/S73A, and F96S/L167V with sequence conservation analysis and comparative analysis of the available apo and holo structures of the enzyme from diverse organisms.