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The ternary alkaline-earth nitridonickelate Ba2[Ni3N2] (Ba2[NiI2Ni0N2]) was prepared by the reaction of mixtures of Ba2N and Ni in nitrogen gas of ambient back-pressure at 1173 K. The crystal structure determined by X-ray single-crystal and powder diffraction methods as well as from neutron diffraction data at various temperatures between 2 and 298 K is orthorhombic (Cmca (no. 64), 298 K: a=715.27(18) pm, b=1032.99(21) pm, c=740.12(20) pm) and provides the first example of a nitridonickelate with a two-dimensional complex anion. The Ni2 atom is described with a split position and the corresponding superstructure variants are investigated by theoretical full-potential nonorthogonal local-orbital calculations (FPLO). The average oxidation state of Ni in Ba2[Ni3N2] is +0.67, the lowest average value observed in nitridonickelates so far. Investigations of the physical properties demonstrate that Ba2[Ni3N2] acts as a "poor" metal with a large resistivity of approximately 2.7 mOmega cm at 300 K and exhibits low-dimensional magnetism with antiferromagnetic ordering at T approximately 90 K. XAS spectra correspond with low-valent Ni states.
Multiple time step (MTS) algorithms present an effective integration approach to reduce the computational cost of dynamics simulations. By using force splitting to allow larger time steps for the more slowly varying force components, computational savings can be realized. The Particle-Mesh-Ewald (PME) method has been independently devised to provide an effective and efficient treatment of the long-range electrostatics interactions. Here we examine the performance of a combined MTS/PME algorithm previously developed for AMBER on a large polymerase beta/DNA complex containing 40,673 atoms. Our goal is to carefully combine the robust features of the Langevin/MTS (LN) methodology implemented in CHARMM-which uses position rather than velocity Verlet with stochasticity to make possible outer time steps of 150 fs-with the PME formulation. The developed MTS/PME integrator removes fast terms from the reciprocal-space Ewald component by using switch functions. We analyze the advantages and limitations of the resulting scheme by comparing performance to the single time step leapfrog Verlet integrator currently used in AMBER by evaluating different time-step protocols using three assessors for accuracy, speedup, and stability, all applied to long (i.e., nanosecond) simulations to ensure proper energy conservation. We also examine the performance of the algorithm on a parallel, distributed shared-memory computer (SGI Origin 2000 with 8 300-MHz R12000 processors). Good energy conservation and stability behavior can be demonstrated, for Newtonian protocols with outer time steps of up to 8 fs and Langevin protocols with outer time steps of up to 16 fs. Still, we emphasize the inherent limitations imposed by the incorporation of MTS methods into the PME formulation that may not be widely appreciated. Namely, the limiting factor on the largest outer time-step size, and hence speedup, is an intramolecular cancellation error inherent to PME. This error stems from the excluded-nonbonded correction term contained in the reciprocal-space component. This cancellation error varies in time and introduces artificial frequencies to the governing dynamics motion. Unfortunately, we find that this numerical PME error cannot be easily eliminated by refining the PME parameters (grid resolution and/or order of interpolating polynomial). We suggest that methods other than PME for fast electrostatics may allow users to reap the full advantages from MTS algorithms.
The papillomavirus E2 proteins are transcriptional regulators that bind to a consensus DNA sequence ACCG NNNN CGGT. Multiple copies of this binding site are found in the viral genomes. The affinities of the naturally occurring binding sites for the E2 proteins are predominantly dependent upon the sequence of the NNNN spacer. The hierarchies of binding site affinities among the sites present in the viral genomes result in differential occupancy during the viral life-cycle. In turn, this differential binding regulates transcription from viral promoters, including those for the oncogenes E6 and E7. Structural and biochemical studies have shown that E2 proteins bend the DNA to which they specifically bind. Atomic resolution structures of complexes of the bovine papillomavirus strain 1 (BPV-1) E2 protein and DNA show that the protein does not contact the spacer DNA. A direct comparison of the binding of the DNA-binding domains of the E2 proteins from BPV-1 and human papillomavirus strain 16 (HPV-16) to a series of binding sites as a function of the sequence of their central spacer and/or the presence of a nick or gap in one strand of the spacer DNA is presented in this paper. The BPV-1 E2 DNA-binding domain is only moderately sensitive to the nature of the central spacer; less than several fold differences in affinity were observed when the DNA sequence of the spacer was varied and/or a nick or gap was introduced. In contrast, the HPV-16 E2 DNA-binding domain binds to sites containing A:T-rich central spacers with significantly increased affinity. The introduction of a nick or gap into the spacer of these high affinity sequences is very detrimental to HPV-16 E2 binding while comparable nicks or gaps have only small effects in the low affinity sequences. These results suggest that the HPV-16 E2 protein recognizes the structure of the DNA spacer and that the mechanism of DNA-sequence specific binding of the homologous HPV-16 E2 and BPV-1 E2 proteins is significantly different.
The crystal structure of Clostridium thermocellum endoglucanase CelA in complex with cellopentaose has been determined at 0.94 A resolution. The oligosaccharide occupies six D-glucosyl-binding subsites, three on either side of the scissile glycosidic linkage. The substrate and product of the reaction occupy different positions at the reducing end of the cleft, where an extended array of hydrogen-bonding interactions with water molecules fosters the departure of the leaving group. Severe torsional strain upon the bound substrate forces a distorted boat(2,5) B conformation for the glucosyl residue bound at subsite -1, which facilitates the formation of an oxocarbenium ion intermediate and might favor the breakage of the sugar ring concomitant with catalysis.
The reduction of Cr(VI) to Cr(III) by glutathione (GSH) in vitro resulted in the formation of two different GSH-chromium complexes with an approximate molecular-weight of 10,000 and 5000, respectively. Both complexes exhibited strong fluorescence. The molar ratio between oxidized glutathione (GSSG) and chromium was calculated by determining the chromium content of the two isolated complex species by flameless Atomic Absorption Spectrometry (AAS).
When skulls and bones were exhumed from a mass grave in Bulgaria and subjected to medicolegal examination they were found to originate from 39 humans aged 36-60 years old who had been buried approximately 45-50 years ago. Solid structures which strongly resembled shrunken human brain tissue were found inside 2 intact skulls. Among other bones 5 similar structures were found one of which was an almost entirely preserved human brain, and the others were fragments from different regions of the human brain. Samples of these structures were immersed in 15% aqueous glycerol solution to soften and were examined by light and electron microscopy. Samples of this material and of fresh human brain were subjected to elementary atomic spectral analysis. These complex studies indicated the samples to be naturally mummified human brain tissue and that this process had occurred due to specific conditions within the cranial cavities after burial.
Intact trichomes of Spirulina platensis were exposed to 1-5 h of low (0.2 mW cm(-2)) or high (0.6 mW cm(-2)) intensity UV-B (280-320 nm) radiation, alone or with photosynthetically active radiation (PAR) of supplemental 50 muE m(-2) s(-1) white light (WL). The mitigating effect of supplemental WL on UV-B induced alterations in Spirulina were investigated by monitoring time-dependent change in photosystem (PS) II mediated O(2) evolution, absorption, circular dichroism (CD) spectra, and ultrastructure. At low intensity, UV-B induced loss in PS II-catalyzed O(2) evolution, but caused no change in the absorption spectrum. At high intensity, UV-B caused a decrease in absorption by phycobilisomes (PBsomes), which was only partly prevented by the presence of low-intensity supplemental WL. The CD spectral analysis revealed that UV-B exposure caused time-dependent enhancement of the negative psi-type bands at 452 and 689 nm, reflecting alterations in the macroaggregation of chlorophyll-protein complexes. This enhancement of negative PS II-type bands was substantially arrested by the presence of supplemental WL exposure, even when UV-B exposure was continued for 5 h. These changes in UV-B-induced CD spectrum suggest alterations in the antenna structure of Spirulina involving both PBsomes and Chlorophyll a. Thus, supplemental low intensity WL arrests, to large extent, the macroaggregation of pigment-protein complexes. Furthermore, the electron micrographs of Spirulina revealed that UV-B exposure caused disorganization of the cellular ultrastructure, while the inclusion of supplemental WL enhanced the formation of air vacuoles in Spirulina. We suggest that the formation of vacuoles by supplemental WL is a protective feature against UV-B.
A computer analysis of several solution methods for secular equations leads to a determination of their optimum conditions. The results contribute to the application of a new preliminary method of frequency assignment to the vibrational study of the heavy atoms coordination sphere in complex biological structures, such as metalporphyrins and adenosine triphosphate.
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An approach to studying the organization of macromolecular complexes using heavy-atom labeling has been developed and applied to the problem of determining the positions of the histone proteins within the nucleosome. The approach is based on the capability of the scanning transmission electron microscope to image heavy atoms. Nucleosomes containing histones labeled with heavy atoms were prepared by lysine modification of selected histones with methyl (methylthio)acetimidate, followed by reconstitution of the modified histones into nucleosomes, and reaction of the reconstituted nucleosomes with chloroglycyl-1-methioninatoplatinum (II). Micrographs of the platinum-labeled nucleosomes were obtained using the scanning transmission electron microscope, and analyzed using both computer and manual techniques. The results of the analysis were 24 A resolution maps of the distribution of high electron scattering density picture elements (representative of platinum atoms) indicating the position of each histone. The significance of those results and the general applicability of the platinum-labeling techniques are discussed. Finally, a description of the histone positions within the nucleosomes is presented and discussed in relation to the current literature on nucleosome structure.
The crystal structure of malate dehydrogenase from Escherichia coli has been determined with a resulting R-factor of 0.187 for X-ray data from 8.0 to 1.87 A. Molecular replacement, using the partially refined structure of porcine mitochondrial malate dehydrogenase as a probe, provided initial phases. The structure of this prokaryotic enzyme is closely homologous with the mitochondrial enzyme but somewhat less similar to cytosolic malate dehydrogenase from eukaryotes. However, all three enzymes are dimeric and form the subunit-subunit interface through similar surface regions. A citrate ion, found in the active site, helps define the residues involved in substrate binding and catalysis. Two arginine residues, R81 and R153, interacting with the citrate are believed to confer substrate specificity. The hydroxyl of the citrate is hydrogen-bonded to a histidine, H177, and similar interactions could be assigned to a bound malate or oxaloacetate. Histidine 177 is also hydrogen-bonded to an aspartate, D150, to form a classic His.Asp pair. Studies of the active site cavity indicate that the bound citrate would occupy part of the site needed for the coenzyme. In a model building study, the cofactor, NAD, was placed into the coenzyme site which exists when the citrate was converted to malate and crystallographic water molecules removed. This hypothetical model of a ternary complex was energy minimized for comparison with the structure of the binary complex of porcine cytosolic malate dehydrogenase. Many residues involved in cofactor binding in the minimized E. coli malate dehydrogenase structure are homologous to coenzyme binding residues in cytosolic malate dehydrogenase. In the energy minimized structure of the ternary complex, the C-4 atom of NAD is in van der Waals' contact with the C-3 atom of the malate. A catalytic cycle involves hydride transfer between these two atoms.
A series of organotin compounds obtained from the reaction of 2,6-diacetylpyridine nicotinoyl- and isonicotinoylhydrazones with tri- and diorganotin chlorides was investigated. The IR and 119Sn NMR spectroscopic characterization of all the compounds is reported, together with the x-ray crystal structure of [SnEt2(H2dapin')]2[SnEt2Cl3]Cl3.2H2O (H2dapin' = 2,6-diacetylpyridine bis(isonicotinoylhydrazone)). The main feature in this compound is the presence of a tin atom in both the complex ionic units. The coordination polyhedron is a pentagonal bipyramid in the cation and a trigonal bipyramid in the anion. Results are discussed concerning the in vitro evaluation of antimicrobial properties and genotoxic potential of the compounds described. In all cases the complexes show a reduced antimicrobial activity as compared to that of the corresponding organotin compound. Genotoxic properties of the ligands, detected in the Ames test, disappear in the complexes.
The thermophilic cyanobacterium Thermosynechococcus elongatus was cultivated under controlled growth conditions using a new type of photobioreactor, allowing us to optimise growth conditions and the biomass yield. A fast large-scale purification method for monomeric and dimeric photosystem II (PSII) solubilized from thylakoid membranes of this cyanobacterium was developed using fast protein liquid chromatography (FPLC). The obtained PSII core complexes (PSIIcc) were analysed for their pigment stoichiometry, photochemical and oxygen evolution activities, as well as lipid and detergent composition. Thirty-six chlorophyll a (Chla), 2 pheophytin a (Pheoa), 9+/- 1 beta-carotene (Car), 2.9+/-0.8 plastoquinone 9 (PQ9) and 3.8+/-0.5 Mn were found per active centre. For the monomeric and dimeric PSIIcc, 18 and 20 lipid as well as 145 and 220 detergent molecules were found in the detergent shell, respectively. The monomeric and dimeric complexes showed high oxygen evolution activity with 1/4 O(2) released per 37-38 Chla and flash in the best cases. Crystals were obtained from dimeric PSIIcc by a micro-batch method. They diffract synchrotron X-rays to a maximum resolution of 2.9-A, resulting in complete data sets of 3.2 A resolution.
The parasite Schistosoma mansoni lacks the de novo pathway for purine biosynthesis and depends on salvage pathways for its purine requirements. Schistosomiasis is endemic in 76 countries and territories and amongst the parasitic diseases ranks second after malaria in terms of social and economic impact and public health importance. The PNP is an attractive target for drug design and it has been submitted to extensive structure-based design. The atomic coordinates of the complex of human PNP with inosine were used as template for starting the modeling of PNP from S. mansoni complexed with inosine. Here we describe the model for the complex SmPNP-inosine and correlate the structure with differences in the affinity for inosine presented by human and S. mansoni PNPs.
A glutathione-sensitive cross-linked polyethylenimine gene vector CLPEI(50%) was specially designed via the cross-linking reaction between the low molecular weight polyethylenimine (PEI(1800)) and dimethyl 3.3'-dithiopropionimidate dihydrochloride (DTBP). The acid-base titration test indicated that CLPEI(50%) still possessed efficient proton sponge effect. The property of CLPEI(50%)-DNA complexes were investigated by atomic force microscopy (AFM) and dynamic light scattering (DLS). CLPEI(50%) induced DNA condensation and formed spherical nanoparticles. The diameter of polyplexes prepared at pH value of 6.0 and 7.4 was about 150 and 260 nm, respectively. It was interesting to find the polyplexes were sensitive to the reductive glutathione (GSH). The CLPEI(50%)-DNA polyplexes prepared at N/P ratio of 10 were unpacked at GSH concentration of 3mm, which was comparable to the intracellular environment. The in vitro cytotoxicity of CLPEI(50%) was also significantly reduced comparing with PEI(25k). The biomimetic CLPEI(50%)-DNA polyplexes with the low cytotoxicity and GSH-sensitive property could be a good candidate for gene delivery.
Nuclear magnetic resonance (NMR) remains the most promising technique for acquiring atomic-resolution information in complex carbohydrates. Significant obstacles to the acquisition of such data are the poor chemical-shift dispersion and artifacts resultant from their degenerate chemical structures. The recent development of ultra-high-field NMR (at 900 MHz and beyond) gives new potential to overcome these problems, as we demonstrate on a hexasaccharide of the highly repetitive glycosaminoglycan hyaluronan. At 900 MHz, the expected increase in spectral dispersion due to higher resonance frequencies and reduction in strong coupling-associated distortions are observed. In addition, the fortuitous molecular tumbling rate of oligosaccharides results in longer T2-values that further significantly enhances resolution, an effect not available to proteins. Combined, the resolution enhancement can be as much as twofold relative to 600 MHz, allowing all 1H-resonances in the hexasaccharide to be unambiguously assigned using standard natural-abundance experiments. The use of ultra-high-field spectrometers is clearly advantageous and promises a new and exciting era in carbohydrate structural biology.