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In order to uncover the structure of these proteins, researchers used a technique called protein crystallography. Like a mosquito trapped in amber, compounds that are crystallized are placed in array in identical positions and ordered so that scientists can target them with X-ray beams and work backwards from the scattering patterns produced to recreate their three-dimensional structures atom by atom. In the first study, a group of researchers from the Structural Biology Center, which is funded by DOE's Office of Science, mapped out a protein responsible for breaking down organic compounds in soil bacteria, an important process for recycling carbon in the ecosystem. The bacteria used, called Acinetobacter, is located mostly in soil and water habitats, where it helps to change aromatic compounds (named for their ring shape) into forms that can be used as food. One of the sources of aromatic compounds found in soil is lignin, a tough polymer that is an essential part of all plants and that's hard for many organisms to digest. "But Acinetobacter can utilize these aromatic compounds as their sole source of carbon," said Andrzej Joachimiak, who co-authored both studies and is the director of the Structural Biology Center and the Midwest Center for Structural Genomics at Argonne. In order for Acinetobacter to break down the aromatic compounds, it needs to produce catabolic enzymes, molecular machines built from an organism's DNA that break down molecules into smaller parts that can be digested. Whether or not membrane transporters and catabolic enzymes are produced falls to the HcaR regulator, a sort of molecular policeman that controls when the genes that code for these enzymes can be activated. Joachimiak and his colleagues found that the regulator works in a cycle, activating genes when aromatic compounds are present and shutting genes down when the compounds are used up. "By nature it is very efficient," Joachimiak said. "If you don't have aromatic compounds inside a cell, the operon is shut down." The research team didn't stop at mapping out the regulator itself; to discover how the cycle worked, they crystalized the HcaR regulator during interactions with its two major inputs: the aromatic compounds and DNA. The group found that when aromatic compounds are not present in the cell, two wings found on either side of the HcaR regulator wrap around the DNA. This action is mirrored on both sides of the regulator, covering the DNA regulatory site and preventing genes from being activated. "This is something that has never been seen before," Joachimiak said. When the aromatic compounds are present, however, they attach themselves to the HcaR regulator, making it so stiff that it can no longer grapple with the DNA. Joachimiak said that this knowledge could help outside of the lab, with applications such as a sensor for harmful pesticides and as a template for converting more carbon in soil. "If we can train bacteria to better degrade lignin and other polymers produced by plants during photosynthesis, more natural carbon sources can be utilized for example for production of biofuels and bioproducts," Joachimiak said. The paper was published earlier this year by the Journal of Biological Chemistry under the title "How Aromatic Compounds Block DNA Binding of HcaR Catabolite Regulator." It was supported by the National Institutes of Health and the U.S. Department of Energy (Office of Biological and Environmental Research). A second paper focuses on a family of proteins identified as DUF89, which stands for "domain unknown function." This family is conserved across all three branches of the phylogenetic tree, which means that it is likely essential to many life forms. DUF89 has been identified as a type of enzyme called a phosphatase, which strips molecules of their phosphate groups. The paper's authors hypothesized that DUF89 proteins use this ability to save useful proteins in a cell from rogue molecules which could alter their structure, making them useless or destructive. The study found that DUF89 proteins use a metal ion, probably manganese, to lure in potentially harmful molecules and a water molecule to break off their phosphate group. DUF89 proteins could have an important role in breaking down a specific type of disruptive molecule: sugar. When the concentration of sugar in blood reaches high levels, simple sugars can have unwanted side reactions with proteins and DNA through a process called glycation. "We always have to deal with these side reactions that happen in our cells, and when we get older, we have an accumulation of these errors in our cells," Joachimiak said. Joachimiak said that this research could help scientists develop DUF89 treatments from non-human sources as a way to combat glycation in the bloodstream. The paper was published on the Nature Chemical Biology website on June 20 under the title "A family of metal-dependent phosphatases implicated in metabolite damage-control." Other authors on the paper were from the University of Florida, the University of Toronto, the University of California-Davis and Brookhaven National Laboratory. It was supported by the National Science Foundation, Genome Canada, the Ontario Genomics Institution, the Ontario Research Fund, the Natural Sciences and Engineering Research Council of Canada, the National Institutes of Health, the C.V. Griffin Sr. Foundation and the U.S. Department of Energy (Office of Basic Energy Sciences and Office of Biological and Environmental Research). Both studies used X-rays from the Advanced Photon Source, a DOE Office of Science User Facility, using beamlines 19-ID and 19-BM. Both also stem from the goal of the Midwest Center for Structural Genomics, which is to discover the structure and function of proteins potentially important to biomedicine. Joachimiak said that despite the new findings from these studies, when it comes to understanding what proteins do, we still have a long way to go. "When we sequence genomes, we can predict proteins, but when we predict those sequences we can only say something about function for about half of them," Joachimiak said. Explore further: New crystallization method to ease study of protein structures More information: Youngchang Kim et al. How Aromatic Compounds Block DNA Binding of HcaR Catabolite Regulator, Journal of Biological Chemistry (2016). DOI: 10.1074/jbc.M115.712067 Lili Huang et al. A family of metal-dependent phosphatases implicated in metabolite damage-control, Nature Chemical Biology (2016). DOI: 10.1038/nchembio.2108


Koch D.,Columbia University | Koch D.,Office of Biological and Environmental Research | Bauer S.E.,Columbia University | Del Genio A.,NASA | And 8 more authors.
Journal of Climate | Year: 2011

The authors simulate transient twentieth-century climate in the Goddard Institute for Space Studies (GISS) GCM, with aerosol and ozone chemistry fully coupled to one another and to climate including a full dynamic ocean. Aerosols include sulfate, black carbon (BC), organic carbon, nitrate, sea salt, and dust. Direct and BCsnow-albedo radiative effects are included. Model BC and sulfur trends agree fairly well with records from Greenland and European ice cores and with sulfur deposition in North America; however, the model underestimates the sulfur decline at the end of the century in Greenland. Global BC effects peak early in the century (1940s); afterward the BC effects decrease at high latitudes of the Northern Hemisphere but continue to increase at lower latitudes. The largest increase in aerosol optical depth occurs in the middle of the century (1940s-80s) when sulfate forcing peaks and causes global dimming. After this, aerosols decrease in eastern North America and northern Eurasia leading to regional positive forcing changes and brightening. These surface forcing changes have the correct trend but are too weak. Over the century, the net aerosol direct effect is 20.41 W m-2, the BC-albedo effect is 20.02 W m-2, and the net ozone forcing is 10.24 W m-2. Themodel polar stratospheric ozone depletion develops, beginning in the 1970s. Concurrently, the sea salt load and negative radiative flux increase over the oceans around Antarctica. Net warming over the century is modeled fairlywell; however, the model fails to capture the dynamics of the observedmidcentury cooling followed by the late century warming.Over the century, 20%ofArcticwarming and snow-ice cover loss is attributed to the BCalbedo effect. However, the decrease in this effect at the end of the century contributes to Arctic cooling. To test the climate responses to sulfate and BC pollution, two experiments were branched from 1970 that removed all pollution sulfate or BC. Averaged over 1970-2000, the respective radiative forcings relative to the full experiment were 10.3 and 20.3 W m-2; the average surface air temperature changes were +0.2° and -0.03°C. The small impact of BC reduction on surface temperature resulted from reduced stability and loss of low-level clouds. © 2011 American Meteorological Society. Source


Schmidt G.A.,NASA | Kelley M.,NASA | Kelley M.,Trinnovim LLC | Nazarenko L.,NASA | And 68 more authors.
Journal of Advances in Modeling Earth Systems | Year: 2014

We present a description of the ModelE2 version of the Goddard Institute for Space Studies (GISS) General Circulation Model (GCM) and the configurations used in the simulations performed for the Coupled Model Intercomparison Project Phase 5 (CMIP5). We use six variations related to the treatment of the atmospheric composition, the calculation of aerosol indirect effects, and ocean model component. Specifically, we test the difference between atmospheric models that have noninteractive composition, where radiatively important aerosols and ozone are prescribed from precomputed decadal averages, and interactive versions where atmospheric chemistry and aerosols are calculated given decadally varying emissions. The impact of the first aerosol indirect effect on clouds is either specified using a simple tuning, or parameterized using a cloud microphysics scheme. We also use two dynamic ocean components: the Russell and HYbrid Coordinate Ocean Model (HYCOM) which differ significantly in their basic formulations and grid. Results are presented for the climatological means over the satellite era (1980-2004) taken from transient simulations starting from the preindustrial (1850) driven by estimates of appropriate forcings over the 20th Century. Differences in base climate and variability related to the choice of ocean model are large, indicating an important structural uncertainty. The impact of interactive atmospheric composition on the climatology is relatively small except in regions such as the lower stratosphere, where ozone plays an important role, and the tropics, where aerosol changes affect the hydrological cycle and cloud cover. While key improvements over previous versions of the model are evident, these are not uniform across all metrics. Key Points Description of the GISS ModelE2 contribution to CMIP5 Impact on evaluation of structural changes in composition and ocean treatment Ocean model choice is an important structural uncertainty © 2014. American Geophysical Union. All Rights Reserved. Source


Jiao C.,University of Michigan | Flanner M.G.,University of Michigan | Balkanski Y.,CEA Saclay Nuclear Research Center | Bauer S.E.,Columbia University | And 30 more authors.
Atmospheric Chemistry and Physics | Year: 2014

Though many global aerosols models prognose surface deposition, only a few models have been used to directly simulate the radiative effect from black carbon (BC) deposition to snow and sea ice. Here, we apply aerosol deposition fields from 25 models contributing to two phases of the Aerosol Comparisons between Observations and Models (AeroCom) project to simulate and evaluate within-snow BC concentrations and radiative effect in the Arctic. We accomplish this by driving the offline land and sea ice components of the Community Earth System Model with different deposition fields and meteorological conditions from 2004 to 2009, during which an extensive field campaign of BC measurements in Arctic snow occurred. We find that models generally underestimate BC concentrations in snow in northern Russia and Norway, while overestimating BC amounts elsewhere in the Arctic. Although simulated BC distributions in snow are poorly correlated with measurements, mean values are reasonable. The multi-model mean (range) bias in BC concentrations, sampled over the same grid cells, snow depths, and months of measurements, are-4.4 (-13.2 to +10.7) ng g−1 for an earlier phase of AeroCom models (phase I), and +4.1 (-13.0 to +21.4) ng g−1 for a more recent phase of AeroCom models (phase II), compared to the observational mean of 19.2 ng g−1. Factors determining model BC concentrations in Arctic snow include Arctic BC emissions, transport of extra-Arctic aerosols, precipitation, deposition efficiency of aerosols within the Arctic, and meltwater removal of particles in snow. Sensitivity studies show that the model-measurement evaluation is only weakly affected by meltwater scavenging efficiency because most measurements were conducted in non-melting snow. The Arctic (60-90° N) atmospheric residence time for BC in phase II models ranges from 3.7 to 23.2 days, implying large inter-model variation in local BC deposition efficiency. Combined with the fact that most Arctic BC deposition originates from extra-Arctic emissions, these results suggest that aerosol removal processes are a leading source of variation in model performance. The multi-model mean (full range) of Arctic radiative effect from BC in snow is 0.15 (0.07-0.25) W m−2 and 0.18 (0.06-0.28) W m−2 in phase I and phase II models, respectively. After correcting for model biases relative to observed BC concentrations in different regions of the Arctic, we obtain a multi-model mean Arctic radiative effect of 0.17 W m−2 for the combined AeroCom ensembles. Finally, there is a high correlation between modeled BC concentrations sampled over the observational sites and the Arctic as a whole, indicating that the field campaign provided a reasonable sample of the Arctic. © 2014 Author (s). Source


News Article
Site: http://phys.org/chemistry-news/

By adding a few water molecules to the GFP chromophore—the part of the molecule responsible for its color—the scientists simulated crystallographic water molecules in GFPs. When water is added, the excited state that generates fluorescence is more stable. Water apparently shuts the channel to electron emissions, effectively shutting off electron autodetachment competition and allowing fluorescence. The scientists' findings provide a more accurate understanding of this extremely useful protein. The two water molecules shown on the December 14 cover of The Journal of Chemical Physics make a huge difference in the behavior of the GFP. In turn, this can lead to eventual control and manipulation of processes where GFP is used. GFPs (see sidebar) are invaluable as markers for monitoring processes in living cells, such as in cancer research, where GFP-labeled cells model how cancer spreads to organs. Their versatility and value has led to the synthesis of new types of GFPs with different colors and new classes of photoactivatable fluorescent proteins for use in ultra-resolution imaging and optical data storage of raw data images from living cells and tissues. The photophysics of GFP and its chromophore depends on its local structure and environment. Despite extensive experimental and computational studies, many open questions remain about the key fundamental variables governing this process. One question is what controls the efficiency of light emission. When GFP absorbs light, only some of the energy is converted into a fluorescent signal, with the rest being lost by a process known as relaxation or deactivation. The fraction of energy emitted as fluorescence versus that lost by relaxation dictates GFP's efficiency. What the PNNL and LSU scientists wanted to know was how the protein's internal environment—in this case, water—affects specific types of relaxation. "We know the relaxation that competes against the fluorescence is critically dependent on the GFP chromophore's local environments, but we don't fully understand the details of why it happens," said PNNL chemical physicist Dr. Xue-Bin Wang, senior author of the article. "If we get rid of surrounding molecules by using the gas phase, the fluorescence goes away. And in solution, no fluorescence occurs at room temperature. But fluorescence returns at low temperatures. Is it caused by the intrinsic electronic structure properties of the chromophore in the protein? Or is it caused by other molecules in its environment? Our results showed it was the latter." GFP is centrally important to modern cell biology. Its discovery and development garnered the 2008 Nobel Prize in Chemistry for scientists Osamu Shimomura, Martin Chalfie, and Roger Tsien. Gaining a fundamental molecular understanding of how GFP works can lead to the ability to control, engineer, or manipulate systems for new applications, such as biosensors, or for advanced imaging. In the cartoons shown here, the GFP molecules are shown in full, and with the side of the surrounding barrel cut away (right) to reveal the chromophore, which is highlighted as a ball-and-stick model. Fluorescence arises when a molecule absorbs certain colors of visible light and then reemits a different, lower energy color. The interactions of the chromophore with its surroundings will dramatically affect the fluorescent properties of GFP, such as the color or intensity of the fluorescence. Researchers are currently trying to understand the underlying physics of these processes. By adding water and comparing the computation with experimental results, the scientists could determine that their theory of the molecules' structure was accurate. The team combined negative ion photoelectron spectroscopy (NIPES) with theoretical calculations to create a probe to identify the exact conformers of clusters of the p-hydroxybenzylidene-2,3-dimethylimidazolinone anion (HBDI-), a model of the GFP chromophore. They used NWChem, an open-source computational chemistry software package supported by the Department of Energy (DOE) Office of Biological and Environmental Research (BER) and developed at PNNL with unique capabilities regarding excited states and structure characterization, and the supercomputer Cascade, at EMSL. In a previous study by Wang and collaborators at the Chinese Academy of Sciences, the GFP chromophore itself was studied in the gas phase. In the current study, the scientists took another step farther by adding the water molecules. The notable addition was the use of advanced computer simulation techniques developed in collaboration with LSU. "In the current paper, the important component was coming up with an accurate theory. In an experiment, when we obtain a signal, we don't 'see' what is happening. Computer simulations using NWChem and EMSL supercomputing resources, give us the necessary details," said co-author Dr. Karol Kowalski. "It's a puzzle," said computational scientist Dr. Marat Valiev, one of the co-authors. "You can't interrogate the protein system as a whole to obtain key molecular-level parameters governing photoresponses of GFP. We have to disassemble it piece by piece, examine each piece, and then put it back together, which is best approached through combining experiment and simulation." The scientists showed that the first few water molecules progressively stabilize the excited state of the chromophore. "This could be an important role of water molecules in GFPs that has not yet been fully explored," said Wang. Explore further: Researchers transform fluorescent proteins into a scaffold for manipulating genes More information: S. H. M. Deng et al. Vibrationally Resolved Photoelectron Spectroscopy of the Model GFP Chromophore Anion Revealing the Photoexcited S State Being Both Vertically and Adiabatically Bound against the Photodetached D Continuum , The Journal of Physical Chemistry Letters (2014). DOI: 10.1021/jz500869b Kiran Bhaskaran-Nair et al. Probing microhydration effect on the electronic structure of the GFP chromophore anion: Photoelectron spectroscopy and theoretical investigations, The Journal of Chemical Physics (2015). DOI: 10.1063/1.4936252

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