Scientific Publications 2006
2006. "Integrated Molecular Signature of Disease: Analysis of Influenza Virus-Infected Macaques through Functional Genomics and Proteomics." Journal of Virology 80(21):10813 (16 pages). doi:10.1128/JVI.00851-06 Abstract Recent outbreaks of avian influenza in humans have stressed the need for an improved non-human primate model of influenza pathogenesis. In order to develop our macaque model, we expanded our in vivo and functional genomics experiments: We focused on the innate immune response at day 2 post-inoculation and on gene expression in affected lung tissue with viral genetic material present; finally, we sought to identify signature genes for early infection in whole blood. For these purposes, we infected six pigtailed macaques with 107 TCID50 of influenza A/Texas/36/91 virus and three control animals with a sham inoculate. We sacrificed one control and two experimental animals at day 2, 4, and 7 and lung tissue was harvested for pathology, gene expression profiling, and proteomics. Additionally, blood was collected for genomics every other day from each animal until its endpoint. Gross and microscopic pathology, immunohistochemistry, viral gene expression by arrays and/or quantitative real-time RT-PCR confirmed successful yet mild infection in all experimental animals. Genomic experiments were performed using second generation macaque-specific oligonucleotide arrays and high-throughput proteomics revealed host response to infection at the protein level. Our data showed dramatic differences in gene expression within the same influenza-induced lesion based on the presence or absence of viral mRNA. We also identified genes tightly co-regulated in peripheral white blood cells and in lung tissue at day 2 post-inoculation. This latter finding opens the possibility of using gene expression arrays on whole blood to detect infection after exposure but prior to onset of symptoms or shedding.
2006. "A Definitive Analysis of the Rydberg and Valence Anti-bonding Character of States in the O K-edge of H2O." Chemical Physics Letters 428(1-3):207-212. doi:10.1016/j.cplett.2006.07.030 Abstract A new method is introduced that provides a definitive analysis of the nature and the extent of the valence anti-bonding and Rydberg character of excited orbitals involved in excitations from core levels to unoccupied bound states. These excitations are observed in X-ray absorption and related spectroscopies. The new method depends on defining pure valence anti-bonding orbitals using, literally, a linear combination of atomic orbitals. Application to the O K-edge excited states of H2O is presented. This analysis is important since Rydberg and valence anti-bonding orbitals will behave differently when a molecule is placed in a condensed environment.
2006. "Effects of Covalency on the p-Shell Photoemission of Transition Metals: MnO." Physical Review. B, Condensed Matter 73(15):155110. Abstract The effect of the solid state environment for an Mn cation in MnO on the Mn 2p and 3p shell X-ray photoemission spectra, XPS, has been investigated using abinitio relativistic wavefunctions for an embedded MnO6 cluster model of MnO. These wavefunctions include many-body effects due to the angular momentum coupling and recoupling of the open shell electrons. They also include the covalent mixing of the metal d orbitals with ligand p orbitals. The treatment of covalency has not been included previously in ab initio theoretical studies of the 2p shell XPS of transition metal complexes. In this work, covalent interactions between the metal and ligands are treated on an equal footing with spin-orbit splittings. The 4-component spinors used in these wavefunctions are optimized separately for the ground and for the 2p and 3p-hole configurations. This orbital relaxation leads to a “closed-shell” inter-atomic screening of the Mn core-hole. The different orbital sets optimized for the ground and core-ionized configurations mean that mutually, non-orthogonal orbital sets are used to determine the matrix elements for the XPS relative intensities. Our treatment of the transition intensities is rigorous and no approximations are introduced to handle the orbital non-orthogonality. The closed-shell screening is important because changes in the XPS obtained for the MnO6 cluster from that obtained for an isolated Mn2+ cation can be directly linked to this screening and to the consequent reduction in the values of certain exchange integrals. The present work is compared to prior, semi-empirical calculations; these comparisons allow us to identify unresolved questions about the origin of certain features of the MnO XPS and to suggest further calculations to resolve these questions.
2006. "Structural Evolution of Anionic Silicon Clusters SiN (20≤N≤45)." Journal of Physical Chemistry A 110(3):908-912. Abstract Results of a combined photoelectron spectroscopy and first-principles density-functional study of SiN - clusters in the size range 20 e N e 45 are reported and discussed. Evidence for a prolate-to-near-spherical shape transition at N ) 27 is presented. It is shown that the tricapped-trigonal-prism (TTP) structural motif Si9 found in most low-lying clusters SiN -, 9 e N e 19, is replaced or augmented by a series of structural motifs consisting of a bulklike “adamantane” fragment plus a magic-number cluster (Si6, Si7, Si10) or TTP Si9 in low-lying prolate clusters SiN -, N g 20. For 28 e N e 45, almost all low-lying near-spherical clusters SiN -adopt “stuffed-cage”-like structures where the cages are homologous to carbon fullerenes in the sense that they are composed of only five- and six-membered rings. However the arrangement of the “stuffing” atoms is not yet diamondlike.
2006. "The Ion Cyclotron Resonance Frequency of Short, Single-Species Plasmas in Penning Traps." Journal of Applied Physics 99 (1 ): Article Number 013306. Abstract We present models that allow us to calculate the effects of various linear and low-order non-linear terms on the E x B drift frequency in a cylindrical Penning trap mass spectrometer. These effects translate directly to shifts in the observed ion cyclotron resonance frequency. We show that nonlinearities in the external electrostatic potential interact with the space charge to affect the observations. Similarly, image charge effects are readily incorporated into our model. The model is then used to describe experimental observations and found to largely account for our observations.
2006. "Modeling the Structure and Electronic Properties of TiO₂ Nanoparticles." Physical Review. B, Condensed Matter 73:205405 1-8. doi:10.1103/PhysRevB.73.205405 Abstract A self-consistent tight-binding method and density functional theory were used to study structures and electronic properties of anatase nanoparticles. Full geometry optimization resulted in both surface relaxation and a slight overall contraction of the nanoparticles. Analyzing electronic properties using electron localization function and Mulliken populations, we found nonbonding electrons at the edges and corners of the nanoparticle. The results of tight-binding and density functional theory calculations are in good agreement, suggesting the tight-binding scheme to be a useful tool for studies of larger nanoparticles in the range of hundreds to thousands of atoms. The self-consistent tight-binding results on nanoparticles of sizes up to 1365 atoms and some structural, electronic, and energetic trends as a function of nanoparticle size are also reported.
2006. "Predicting the Shape and Structure of Face-Centered Cubic Gold NanocrystalsSmaller than 3 nm." Chemphyschem 7(7):1544-1553. doi:10.1002/cphc.200600107 Abstract Although a number of computational studies have examined the relative stability of icosahedral and decahedral gold clusters from 1 to 3 nm in size, few studies have focussed on the variety of face-centered cubic (fcc)nanoparti cles in this size regime. In most cases small fcc gold particles are assumed to adopt the truncated octahedral shape, but in light of the fact that the shape and structure of gold nanoparticles is known to vary, the relative stability of fcc polyhedra may change with size. Presented here are results of first-principles calculations investigating the preferred shape of gold particles less than 3 nm in size. Our results indicate that the equilibrium shape of fcc gold nanoparticles less than 1 nm is the cuboctahedron, but this shape rapidly becomes energetically unstable with respect to the truncated octahedron, octahedron and truncated cube shapes as the size increases.
2006. "Substitutional Boron in Nanodiamond, Bucky-Diamond, and Nanocrystalline DiamondGrain Boundaries." Journal of Physical Chemistry B 110(39):19307-19314. doi:10.1021/jp0634252 Abstract Although boron has been known for many years to be a successful dopant in bulk diamond, efficient doping of nanocrystalline diamond with boron is still being developed. In general, the location, configuration, and bonding structure of boron in nanodiamond is still unknown, including the fundamental question of whether it is located within grains or grain boundaries of thin films and whether it is within the core or at the surface of nanoparticles. Presented here are density functional tight-binding simulations examining the configuration, potential energy surface, and electronic charge of substitutional boron in various types of nanocrystalline diamond. The results predict that boron is likely to be positioned at the surface of isolated particles and at the grain boundary of thin-film samples.
2006. "Surface Science and the Advancement of Direct Olefin EpoxidationA Perspective on the Article, ‘‘Partial Oxidation of Higher Olefinson Ag(111) and Ag(110): Conversion of Styrene to Styrene Oxide,Benzene, and Benzoic Acid’’, by Andreas Klust and Robert J. Madix." Surface Science 600(23):5021-5023. doi:10.1016/j.susc.2006.09.024 Abstract The research described in this product was performed in part in the Environmental Molecular Sciences Laboratory, a national scientific user facility sponsored by the Department of Energy's Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory. Few reactions are as conceptually simple or as devilishly difficult as the epoxidation of ethylene to form ethylene oxide:
2006. "Conformational Transitions in RNA Single Uridine and Adenosine Bulge Structures: A Molecular Dynamics Free Energy Simulation Study." Biophysical Journal 90(7):2450-2462. doi:10.1529/biophysj.105.076158 Abstract No abstract is available at this time for this article.
2006. "Site-Specific Laser Modification of MgO nanoclusters: Towards Atomic-Scale Surface Structuring." Physical Review. B, Condensed Matter 74:045404 (5 pages). Abstract Atomic emission from MgO nanostructures is induced using laser light tuned to excite specific surface sites at energies well below the excitation threshold of the bulk material. We find that near UV excitation of MgO nancrystalline films and nanocube samples desorbs neutral Mg-atoms with hyper-thermal kinetic energies in the range of 0.1-0.4 eV. Our ab initio calculations suggest that metal atom emission is induced predominantly by electron trapping at surface 3-coordinated Mg sites followed by electronic excitation at these sites. The proposed general mechanism can be used to control atomic scale modification of insulating surfaces.
2006. "Facile Syntheses of Monodisperse Ultra-Small Au Clusters." Journal of Physical Chemistry B 110(43):21416-21418. doi:10.1021/jp065227g Abstract During our effort to synthesize the tetrahedral Au20 cluster, we found a facile synthetic route to prepare monodisperse suspensions of ultra-small Au clusters AuN (N<12) using diphosphine ligands. In our monophasic and single-pot synthesis, a Au precursor ClAu(I)PPh3 and a bidentate phosphine ligand P(Ph)2(CH2)MP(Ph)2 (Ph = phenyl) are dissolved in an organic solvent. Au(I) is reduced slowly by a borane-tert-butylamine complex to form Au clusters coordinated by the diphosphine ligand. The Au clusters are characterized by both high resolution mass spectrometry and UV-Vis absorption spectroscopy. We found that the mean cluster size obtained depends on the chain length M of the ligand. In particular, a single monodispersed Au11 cluster is obtained with the P(Ph)2(CH2)3P(Ph)2 ligand, whereas P(Ph)2(CH2)MP(Ph)2 ligands with M = 5 and 6 yield Au10 and Au8 clusters. The simplicity of our synthetic method makes it suitable for large-scale production of nearly monodisperse ultrasmall Au clusters. It is suggested that diphosphines provide a set of flexible ligands to allow size-controlled synthesis of Au nanoparticles.
2006. "Bond-valence methods for pKa prediction. II. Bond-valence, electrostatic, molecular geometry, and solvation effects ." Geochimica et Cosmochimica Acta 70(16):4057-4071. doi:10.1016/j.gca.2006.06.006 Abstract In a previous contribution, we outlined a method for predicting (hydr)oxy-acid and oxide surface acidity constants based on three main factors: bond valence, Me–O bond ionicity, and molecular shape. Here electrostatics calculations and ab initio molecular dynamics simulations are used to qualitatively show that Me–O bond ionicity controls the extent to which the electrostatic work of proton removal departs from ideality, bond valence controls the extent of solvation of individual functional groups, and bond valence and molecular shape controls local dielectric response. These results are consistent with our model of acidity, but completely at odds with other methods of predicting acidity constants for use in multisite complexation models. In particular, our ab initio molecular dynamics simulations of solvated monomers clearly indicate that hydrogen bonding between (hydr)oxo-groups and water molecules adjusts to obey the valence sum rule, rather than maintaining a fixed valence based on the coordination of the oxygen atom as predicted by the standard MUSIC model.
2006. "Soft X-Ray Microscopy and Spectroscopy at the Molecular Environmental Science Beamline at the Advanced Light Source." Journal of Electron Spectroscopy and Related Phenomena 150(2-3):86-104. Abstract We present examples of the application of synchrotron-based spectroscopies and microscopies to environmentally-relevant samples. The experiments were performed at the Molecular Environmental Science beamline (11.0.2) at the Advanced Light Source, Lawrence Berkeley National Laboratory. Examples range from the study of water monolayers on Pt(111) single crystal surfaces using X-ray emission spectroscopy and the examination of alkali halide solution/water vapor interfaces using ambient pressure photoemission spectroscopy, to the investigation of actinides, river-water biofilms, Al-containing colloids and mineral-bacteria suspensions using scanning transmission X-ray spectromicroscopy. The results of our experiments show that spectroscopy and microscopy in the soft X-ray energy range are excellent tools for the investigation of environmentally relevant samples under realistic conditions, i.e. with water or water vapor present at ambient temperature.
2006. "Gold as Hydrogen: Structural and Electronic Properties and Chemical Bonding in Si3Au3=/01- and Comparisons to Si3H3=/o1-." Journal of Chemical Physics 125(13):Art. No.133204. doi:10.1063/1.2216707 Abstract A single Au atom has been shown to behave like H in its bonding to Si in several mono- and disilicon gold clusters. In the current work, we investigate the Au/H analogy in trisilicon gold clusters, Si3Au3 +/0/−. Photoelectron spectroscopy and density functional calculations are combined to examine the geometric and electronic structure of Si3Au3−. We find that there are three isomers competing for the ground state of Si3Au3− as is the case for Si3H3 −. Extensive structural searches show that the potential energy surfaces of the trisilicon gold clusters _Si3Au3 −, Si3Au3, and Si3Au3+_ are similar to those of the corresponding silicon hydrides. The lowest energy isomers for Si3Au3 − and Si3Au3 are structurally similar to a Si3Au four-membered ring serving as a common structural motif. For Si3Au3 +, the 2 _ aromatic cyclotrisilenylium auride ion, analogous to the aromatic cyclotrisilenylium ion _Si3H3 +_, is the most stable species. Comparison of the structures and chemical bonding between Si3Au3 +/0/− and the corresponding silicon hydrides further extends the isolobal analogy between Au and H.
2006. "A Combined FTIR and TPD Study on the Bulk and Surface Dehydroxylation and Decarbonation of Synthetic Goethite." Geochimica et Cosmochimica Acta 70(14):3613-3624. Abstract The thermal dehydroxylation of dried goethite was studied with combined Fourier Transform Infrared (FTIR)-Temperature Programmed Desorption (TPD) experiments in the presence and absence of adsorbed carbonate and oxalate. The TPD data revealed a dehydroxylation peaks involving the intrinsic dehydroxylation of goethite at 575 K but also a low temperature peak at 475 K which was shown to be associated to the release of non-stoichiometric water in the goethite bulk and surface. The FTIR and the TPD data of goethite in the absence of adsorbed species revealed the presence of adventitious carbonate mostly sequestered in the goethite bulk. The release of carbonate was however not only related to the dehydration of goethite but also to the compaction of the hematite phase at temperatures exceeding 700 K. The relative abundance of surface hydroxyls was shown to change systematically upon goethite dehydroxylation with a preferential stripping of -OH sites followed by a dramatic change in the dominance of the different surface hydroxyls upon the crystallization of hematite. The presence of surface-bound carbonate revealed similar FTIR bands as those of bulk-carbonate, suggesting similar bonding structures. The release of surface-bound carbonate was moreover shown to be associated to the low temperature dehydration peak and concomitantly with the preferential stripping of –OH sites more than 100 K below the dehydroxylation edge of goethite. The presence of chemisorbed oxalate species produced an important release of CO at 425 K, followed by the presence of a transient carbonyl-bearing surface species (e.g. oxalate of different coordination geometry or formate) which were subsequently decomposed to formic acid and CO2 at higher temperatures. The thermal decomposition of oxalate/formate did not, however, reveal additional adsorbed CO2(g) at the goethite surface.
2006. "Formation of Monodisperse (WO3)3 Clusters on Ti02(110)." Angewandte Chemie International Edition 45(29):4786-4789. doi:10.1002/anie.200600837 Abstract Monodisperse, adsorbed cyclic trimers of WO3 have been prepared and characterized. Powdered WO3 was sublimed onto TiO2(110) at 300 K. After annealing to 600 K, scanning tunneling microscopy (STM) images indicated monodispersity, X-ray photoelectron spectroscopy indicated fully oxidized W6+, and mass microbalance, coupled with STM, indicated that each nanocluster was (WO3)3. Within the STM image of each adsorbed nanocluster, there was structure ascribed, on the basis of density functional theory, to characteristic low-lying unoccupied molecular orbitals of the cyclic isomer of (WO3)3.
2006. "In Situ Infrared Study of the Catalytic Ignition of Methane on Pt/Al2O3." Applied Catalysis. A, General 224-231. doi:10.1016/j.apcata.2006.01.008 Abstract The ignition process of the partial oxidation of methane over Pt/Al2O3 catalysts has been investigated at atmospheric pressure using in situ DRIFT spectroscopy. Contacting methane with the catalyst shows that the dissociative adsorption of methane, evidenced by the appearance of the linearly adsorbed CO species, is delayed to higher temperatures for an oxygen-covered surface compared to an oxygen-free surface. Carbonate species were progressively obtained on the surface before the ignition temperature when interacting CH4/O2/He mixtures with the catalyst. They result from the interaction of produced carbon dioxide with the support. The temperature at which the carbonate species appears is lower for lower concentration of oxygen in the mixture. It has been shown that oxygen is mainly covering the surface until the ignition temperature. Competition between the two reactants is therefore assumed. It has been found that the state of platinum has a large effect on the ignition temperature, with the highest ignition temperature found for oxidized sample (platinum particle diameter, DPt = 1.9–2.2 nm), the next highest for freshly reduced sample (DPt = 1.7–1.9 nm), and the lowest on aged sample (DPt = 4–5 nm). All of these results linked to microcalorimetry measurements and literature data suggest that the heat of adsorption of oxygen is a key factor for ignition of the surface reaction.
2006. "High-field QCPMG NMR of Strontium Nuclei in Natural Minerals." Solid State Nuclear Magnetic Resonance 29(1-3):95-103. Abstract This work was supported by the United States Department of Energy under grant number DE-FG07-99ER15012. ASL would like to acknowledge support from the National Institutes of Health (Federal grant EB002050) and the United States Department of Energy Office of Biological and Environmental Research Program (KP13-01-03-0-22142). GMB would like to thank Joseph Ford for assistance with the experimental aspects of the 900 MHz instrument. Part of the research described in this paper was performed in the Environmental Molecular Sciences Laboratory, a national scientific user facility sponsored by the Department of Energy's Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory. Support for the 11.74 T spectrometer at Penn State was provided by NSF grant CHE-9601572. Currently, the direct observation of strontium with solid-state nuclear magnetic resonance (NMR) is experimentally challenging. Strontium has a single NMR-active isotope (87Sr) that is quadrupolar (I = 9/2) with a low gyromagnetic ratio ( = -1.163x107 T-1 s-1) and a low natural abundance (~7%); factors which imply low sensitivity. Strontium nuclei located at lattice sites with moderate electric field gradients have been reported to possess large quadrupolar coupling constants, leading to broad resonances that further reduce sensitivity and limit the effectiveness of magic-angle spinning (MAS) experiments.[1, 2] In order to study strontium in samples where strontium nuclei are sparse, such as clays and zeolites, methods to enhance the sensitivity of 87Sr NMR must undergo further development.
2006. "NMR Study of Strontium Binding by a Micaceous Mineral." Journal of Physical Chemistry B 110(14):7159-7164. Abstract The nature of strontium binding by soil minerals directly affects the transport and sequestration/remediation of radioactive strontium species released from leaking high-level nuclear waste storage tanks. However, the molecular-level structure of strontium binding sites has seldom been explored in phyllosilicate minerals by direct spectroscopic means and is not well-understood. In this work, we use solid-state NMR to analyze strontium directly and indirectly in a fully strontium-exchanged synthetic mica of nominal composition Na4Mg6Al4Si4O20F4. Thermogravimetric analysis, X-ray diffraction analysis, and NMR evidence supports that heat treatment at 500 °C for 4 h fully dehydrates the mica, creating a hydrogen-free interlayer. Analysis of the strontium NMR spectrum of the heat-treated mica shows a single strontium environment with a quadrupolar coupling constant of 9.02 MHz and a quadrupolar asymmetry parameter of 1.0. These quadrupolar parameters are consistent with a highly distorted and asymmetric coordination environment that would be produced by strontium cations without water in the coordination sphere bound deep within the ditrigonal holes. Evidence for at least one additional strontium environment, where proton-strontium couplings may occur, was found via a 1H-87Sr transfer of populations by double resonance NMR experiment. We conclude that the strontium cations in the proton-free interlayer are observable by 87Sr NMR and bound through electrostatic interactions as nine coordinate inner-sphere complexes sitting in the ditrigonal holes. Partially hydrated strontium cations invisible to direct 87Sr NMR are also present and located on the external mica surfaces, which are known to hydrate upon exposure to atmospheric moisture. These results demonstrate that modern pulsed NMR techniques and high fields can be used effectively to provide structural details of strontium binding by phyllosilicate minerals.
2006. "Deinococcus radiodurans Engineered for Complete Toluene Degradation Facilitates Cr(VI) Reduction." Microbiology 152(8):2469-2477. Abstract Toluene and other fuel hydrocarbons are commonly found in association with radionuclides at numerous US Department of Energy sites, frequently occurring together with Cr(VI) and other heavy metals. In this study, the extremely radiation-resistant bacterium Deinococcus radiodurans, which naturally reduces Cr(VI) to the less mobile and less toxic Cr(III), was engineered for complete toluene degradation by cloned expression of tod and xyl genes of Pseudomonas putida. The recombinant Tod/Xyl strain showed incorporation of carbon from 14C-labelled toluene into cellular macromolecules and carbon dioxide, in the absence or presence of chronic ionizing radiation. The engineered bacteria were able to oxidize toluene under both minimal and complex nutrient conditions, and recombinant cells reduced Cr(VI) in sediment microcosms. As such, the Tod/Xyl strain could provide a model for examining the reduction of metals coupled to organic contaminant oxidation in aerobic radionuclide-contaminated sediments.
2006. "Conformational Preferences and Internal Rotation in Alkyl- and Phenyl-Substituted Thiourea Derivatives." Journal of Physical Chemistry A 110(14):4678-4688. doi:10.1021/jp056906e Abstract Potential energy surfaces (PES) for rotation about the N-C(sp3) or N-C(aryl) bond and energies of stationary points on PES for rotation about the C(sp2)-N bond are reported for methylthiourea, ethylthiourea, isopropylthiourea, t-butylthiourea, and phenylurea, using the MP2/aug-cc-pVDZ method. Analysis of alkylthioureas shows that conformations, with alkyl groups cis to the sulfur atom are more stable (by 0.4 to 1.5 kcal/mol) than the trans forms. All minima adopt anti configurations with respect to nitrogen pyramidalization, whereas syn configurations are not stationary points on the MP2 potential surface. In contrast, analysis of phenylthiourea reveals that a trans isomer in a syn geometry is the global minimum, whereas a cis isomer in an anti geometry is a local minimum with a relative energy of 2.7 kcal/mol. Rotation about the C(sp2)-N bond in alkyl and phenyl thioureas is slightly more hindered (9.1-10.2 kcal/mol) than the analogous motion in the unsubstituted molecule (8.6 kcal/mol). The maximum barriers to rotation for the methyl, ethyl, isopropyl, t-butyl and phenyl substituents are predicted to be 1.2, 8.9, 8.6, 5.3, and 0.9 kcal/mol, respectively. Corresponding PESs are consistent with the experimental dihedral angle distribution observed in crystal structures. The results of the electronic structure calculations are used to benchmark the performance of the MMFF94 force field. Systematic discrepancies between MMFF94 and MP2 results were improved by modification of selected torsion parameters and one of the van der Waals parameters for sulfur.
2006. "De novo structure-based design of bisurea hosts for tetrahedral oxyanion guests." Journal of the American Chemical Society 128(6):2035-2042. Abstract This paper presents a computational approach to the deliberate design of improved host architectures. De novo molecule building software, HostDesigner, is interfaced with molecular mechanics software, GMMX, providing a tool for generating and screening millions of potential structures. The efficacy of this computer-aided design methodology is illustrated with a search for bis-urea podands that are structurally organized for complexation with tetrahedral oxyanions.
2006. "A UbcH5/Ubiquitin Noncovalent Complex is Required for Processive BRCA1-Directed Ubiquitination." Molecular Cell 21(6):873-880. Abstract Protein ubiquitination is a powerful regulatory modification that influences nearly every aspect of eukaryotic cell biology. The general pathway for ubiquitin (Ub) modification requires the sequential activities of a Ub-activating enzyme (E1), a Ub transfer enzyme (E2), and a Ub ligase (E3). The E2 must recognize both the E1 and a cognate E3 in addition to carrying activated Ub. These central functions are performed by a topologically conserved a/b-fold core domain ofw150 residues shared by all E2s. However, as presented herein, the UbcH5 family of E2s can also bind Ub noncovalently on a surface well removed from the E2 active site. We present the solution structure of the UbcH5c/ Ub noncovalent complex and demonstrate that this noncovalent interaction permits self-assembly of activated UbcH5cwUb molecules. Self-assembly has profound consequences for the processive formation of polyubiquitin (poly-Ub) chains in ubiquitination reactions directed by the breast and ovarian cancer tumor susceptibility protein BRCA1
2006. "Characterization of two potentially universal turn motifs that shape the repeated five-residues fold - Crystal structure of a lumenal pentapeptide repeat protein from Cyanothece 51142." Protein Science 15(11):2579-2595. Abstract The genome of the diurnal cyanobacterium Cyanothece sp. PCC 51142 has recently been sequenced and observed to contain 35 pentapeptide repeat proteins (PRPs). These proteins, while present throughout the prokaryotic and eukaryotic kingdoms, are most abundant in cyanobacteria. The sheer number of PRPs in cyanobacteria coupled with their predicted location in all the cyanobacteria cellular compartments argues for important, yet unknown, physiological and biochemical functions. To gain insights into the biochemical function of PRPs in cyanobacteria, the first crystal structure of a PRP from Cyanothece has been determined at 2.1 Å resolution. The native protein, annotated Rfr32 for repeated five-residue, is a 167-residue protein with an N-terminal 29-residue signal peptide. The signal peptide was replaced with a 43-residue tag that was invisible in the electron density maps of two different crystal forms from which essentially identical structures were solved. The structure is dominated by 21 tandem pentapeptide repeats that fold into a right-handed quadrilateral β-helix, or Rfr-fold, reminiscent of a “square” tower with four distinct faces. Four consecutive pentapeptide repeats define a “floor” of the tower with a single repeat occupying a face. The Rfr-fold contains five complete, stacked, ascending floors (coils) that complete a revolution every 20 residues with a ~4.8 Å rise along the helix axis. The main chain backbone of the floors are held together with a narrow parallel β-sheet on one face and stacked parallel The main chain backbone of the floors are held together with a narrow parallel β-sheet on one face and stacked parallel β-bridges (single-residue β-sheets) on the other three faces. The regular shape of the tower is maintained by two distinct types of four-residue turns labeled pseudo type II and pseudo type IV β-turns. The interior of the Rfr-fold is primarily hydrophobic, with all side chains of the i and i-2 residues inserted into the center of the β-helix to form aligned, stacked, columns of hydrophobic side chains. The i-1, i+1, and i+2 residues are generally polar or charged and these side chains all point away from the Rfr-core to give the β-helix a predominately hydrophilic surface. Two short, anti-parallel β-helices, bridged with a disulfide bond, sit atop of the C-terminus of the Rfr-fold perhaps preventing edge-to-edge aggregation at the C-terminus of the Rfr-fold. The circular dichroism spectra of Rfr-32 is dominated by β-turn and parallel β-sheet features. The structure of Rfr32 is compared with the only other PRP structure, the mycobacterial fluoroquinoline resistance protein MfpA from Mycobacterium tuberculosis, and the general features of the amino acid sequences of the 35 Cyanothece PRPs are discussed.
2006. "Cloning, expression, crystallization and preliminary crystallographic analysis of a pentapeptide-repeat protein (Rfr23) from bacterium Cyanothece 511421." Acta Crystallographica. Section F 62(12):1251-1254. doi:10.1107/S174430910604663X Abstract A unique feature of cyanobacteria genomes is the abundance of genes that code for hypothetical proteins containing tandem pentapeptide repeats approximately described by the consensus motif A[N/D]LXX. Too date, structures of two pentapeptide repeat proteins (PRPs) have been determined with the tandem pentapeptide repeat sequences observed to adopt a novel right-handed quadrilateral b-helix, or Rfr-fold, in both structures. One structure, Mycobacterium tuberculosis MfpA, is a 183-residue protein that contains 30 consecutive pentapeptide repeats and appears to offer antibiotic resistance by acting as a DNA mimic. The other structure, Cyanothece Rfr32, is a 167-residue protein that contains 21 consecutive pentapeptide repeats. The function of Rfr32, like the other 35 hypothetical PRPs identified in the genome of Cyanothece, is unknown. In an effort to understand the role of PRPs in cyanobacteria, and to better characterize the structural properties of Rfr-folds with different amino acid sequences, a second PRP from Cyanothece 51142, Rfr23, has been cloned, expressed, and purified. Selenomethione substituted protein was crystallized by vapor diffusion in hanging drops. MAD diffraction data were collected on these crystals to 2.? Å resolution using synchrotron radiation. The crystals belonged to space group I41 with unit-cell parameters a = b = 106.23 Å, c = 52.40 Å. Analysis of the 172-residue protein sequence suggests that Rfr23 contains 26 pentapeptide repeats interrupted by eight residues near the N-terminus. The electron density map suggests that the pentapeptide repeats adopt a similar right-handed quadrilateral b-helix as observed in the other two PRP structures, however, the eight residue interruption in the string of pentapeptide repeats appears to create a distortion in the Rfr-fold.
2006. "Solution Structure of the Conserved Hypothetical Protein Rv2302 from Mycobacterium tuberculosis. ." Journal of Bacteriology 188(16):5993-6001. doi:10.1128/JB.00460-06 Abstract The hypothetical Mycobacterium tuberculosis protein RV2302 (80 residues, MW = 8.6 kDa) has been characterized using nuclear magnetic resonance (NMR) and circular dichroism (CD) spectroscopy. Size exclusion chromatography and NMR spectroscopy suggest that RV2302 is as a monomer is solution. Circular dichroism spectroscopy indicates the protein is structured in solution, but, irreversible unfolds upon heating with an inflection point of ~48°C. Using NMR based methods we determined the solution structure of RV2302. The protein contains a five strand, anti-parallel b-sheet core with one C-terminal a-helix (A65-A75) nestled against its side. Dali searches using the structure closest to the average structure did not identify any high similarities to any other known protein structure. Consequently, the structure of Rv2302 may potentially represent a novel protein fold.
2006. "Evidence of Hollow Golden Cages." Proceedings of the National Academy of Sciences of the United States of America 103(22):8326-8330. doi:10.1073/pnas.0600637103 Abstract The fullerenes are the first “free-standing” elemental hollow cages identified by spectroscopy experiments and synthesized in the bulk. Here we report experimental and theoretical evidence of hollow cages consisting of pure metal atoms, Aun ¯ (n = 16-18), which, to our knowledge, are the first free-standing metal hollow cages detected in the laboratory. These hollow golden cages have an average diameter larger than 6 Å, which can easily hold one foreign atom inside.
2006. "Lowest-energy structures of water clusters (H2O)(11) and (H2O)(13)." Journal of Physical Chemistry A 110(42):11781-11784. Abstract We employed a four-step searching/screening approach to determine best candidates for the global minima of (H2O)11 and (H2O)13. This approach can be useful when there exist a large number of low-lying and near-isoenergetic isomers, many of which have the same oxygen-skeleton structure. On the two new candidates for the global minimum of (H2O)11, one isomer can be viewed as placing the 11th molecule onto the side of the global minimum of (H2O)10 while the other can be viewed as removing the 12th molecule from the middle layer of the global minimum of (H2O)12. The three leading lowest-energy clusters of (H2O)13 can all be built upon the global minimum of (H2O)12, with the difference in the location of the 13th water molecule. This research was performed in part using the Molecular Science Computing Facility in the William R. Wiley Environmental Molecular Sciences Laboratory, a national scientific user facility sponsored by DOE’s Office of Biological and Environmental Research.
2006. "Estimating The Thermodynamics And Kinetics Of Chlorinated Hydrocarbon Degradation." Theoretical Chemistry Accounts 116(1-3):281-296. doi:10.1007/s00214-005-0042-8 Abstract Many different degradation reactions of chlorinated hydrocarbons are possible in natural ground waters. In order to identify which degradation reactions are important, a large number of possible reaction pathways must be sorted out. Recent advances in ab initio electronic structure methods have the potential to help identify relevant environmental degradation reactions by characterizing the thermodynamic properties of all relevant contaminant species and intermediates for which experimental data is usually not available, as well as provide activation energies for relevant pathways. In this paper, strategies based on ab initio electronic structure methods for estimating thermochemical and kinetic properties of reactions with chlorinated hydrocarbons are presented. Particular emphasis is placed on strategies that are computationally fast and can be used for large organochlorine compounds such as 4,4’-DDT.
2006. "New Development of Self-Interaction Corrected DFT for Extended Systems Applied to the Calculation of Native Defects in 3C-SiC." Physica Scripta T124:86-90. Abstract We recently have developed a framework for implementing a scaled self-interaction corrected density functional theory (DFT-SIC) into pseudopotential plane-wave DFT. The technique implements the original method due to Perdew and Zunger by direct minimization of the DFT-SIC total energy functional. By using maximally localized Wannier functions, DFT-SIC calculation can be carried out efficiently even for extended systems. Using this new development the formation energies of defects in 3C-SiC were calculated and compared to more standard DFT calculations. Differences of up to 1eV were seen between DFT and DFT-SIC calculations of the formation energies. When compared to DFT, DFT-SIC produced less stable vacancies and silicon interstials, more stable antisites and carbon interstitials. The most favorable interstitials were found to be C interstitials in a C+-C<100> dumbbell configuration, with the formation energy of 5.91eV with DFT and 5.65 eV with DFT-SIC. Si interstitials were not as stable as C interstitials. The most favorable Si interstitial was found to be Si tetrahedral surrounded by four C atoms, with a formation energy of 7.65eV with DFT and 8.71eV with DFT-SIC.