Department of Chemistry Biochemistry

Recent Publications

May 8, 2015

"Methadone Contributes to N-Nitrosodimethylamine Formation in Surface Waters and Wastewaters during Chloramination", David Hanigan , E. Michael Thurman, Imma Ferrer, Yang Zhao, Susan Andrews, Jinwei Zhang, Pierre Herckes , and Paul Westerhoff, Environ. Sci. Technol. Lett., Article ASAP, DOI: 10.1021/acs.estlett.5b00096 Publication Date (Web): May 8, 2015.

February 17, 2015

"Quantification of graphene and graphene oxide in complex organic matrices", Kyle Doudrick, Takayuki Nosaka, Pierre Herckes, Paul Westerhoff, Environ. Sci.: Nano, 2015,2, 60-67, DOI: 10.1039/C4EN00134F


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January 19, 2015

"Prevalent and distinct spliceosomal 3'-end processing mechanisms for fungal telomerase RNA", Xiaodong Qi, Dustin P. Rand, Joshua D. Podlevsky, Yang Li, Axel Mosig, Peter F. Stadler & Julian J. -L. Chen, Nature Communications 6, Article number: 6105, doi:10.1038/ncomms7105, Published 19 January 2015

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December 4, /2014
New research paves the way for nano-movies of biomolecules

Scientists use X-ray laser as ultra slow-motion camera

"Time-resolved serial crystallography captures high-resolution intermediates of photoactive yellow protein" Science 5 December 2014, Vol. 346 no. 6214 pp. 1242-1246 DOI: 10.1126/science.1259357

Asteroid impacts on Earth make structurally bizarre diamonds, say ASU scientists

"Lonsdaleite is faulted and twinned cubic diamond and does not exist as a discrete material", Péter Németh, Laurence A. J. Garvie, Toshihiro Aoki, Natalia Dubrovinskaia, Leonid Dubrovinsky & Peter R. Buseck, Nature Communications 5, Article number: 5447, doi:10.1038/ncomms6447, 20 November 2014

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July 9, 2014
ASU-led study yields first snapshots of water splitting in photosynthesis

Photosynthesis, a process catalysed by plants, algae and cyanobacteria converts sunlight to energy thus sustaining all higher life on Earth. Two large membrane protein complexes, photosystem I and II (PSI and PSII), act in series to catalyse the light-driven reactions in photosynthesis. PSII catalyses the light-driven water splitting process, which maintains the Earth's oxygenic atmosphere1. In this process, the oxygen-evolving complex (OEC) of PSII cycles through five states, S0 to S4, in which four electrons are sequentially extracted from the OEC in four light-driven charge-separation events. Here we describe time resolved experiments on PSII nano/microcrystals from Thermosynechococcus elongatus performed with the recently developed2 technique of serial femtosecond crystallography. Structures have been determined from PSII in the dark S1 state and after double laser excitation (putative S3 state) at 5 and 5.5 Å resolution, respectively. The results provide evidence that PSII undergoes significant conformational changes at the electron acceptor side and at the Mn4CaO5 core of the OEC. These include an elongation of the metal cluster, accompanied by changes in the protein environment, which could allow for binding of the second substrate water molecule between the more distant protruding Mn (referred to as the 'dangler' Mn) and the Mn3CaOx cubane in the S2 to S3 transition, as predicted by spectroscopic and computational studies3, 4. This work shows the great potential for time-resolved serial femtosecond crystallography for investigation of catalytic processes in biomolecules.

"Serial time-resolved crystallography of photosystem II using a femtosecond X-ray laser", Christopher Kupitz, Shibom Basu, Ingo Grotjohann, Raimund Fromme, Nadia A. Zatsepin, Kimberly N. Rendek, Mark S. Hunter, Robert L. Shoeman, Thomas A. White, Dingjie Wang, Daniel James, Jay-How Yang, Danielle E. Cobb, Brenda Reeder, Raymond G. Sierra, Haiguang Liu, Anton Barty, Andrew L. Aquila, Daniel Deponte, Richard A. Kirian, Sadia Bari, Jesse J. Bergkamp, Kenneth R. Beyerlein, Michael J. Bogan, Carl Caleman, Tzu-Chiao Chao, Chelsie E. Conrad, Katherine M. Davis, Holger Fleckenstein, Lorenzo Galli, Stefan P. Hau-Riege, Stephan Kassemeyer, Hartawan Laksmono, Mengning Liang, Lukas Lomb, Stefano Marchesini, Andrew V. Martin, Marc Messerschmidt, Despina Milathianaki, Karol Nass, Alexandra Ros, Shatabdi Roy-Chowdhury, Kevin Schmidt, Marvin Seibert, Jan Steinbrener, Francesco Stellato, Lifen Yan, Chunhong Yoon, Thomas A. Moore, Ana L. Moore, Yulia Pushkar, Garth J. Williams, Sébastien Boutet, R. Bruce Doak, Uwe Weierstall, Matthias Frank, Henry N. Chapman, John C. H. Spence & Petra Fromme, Nature (2014) doi:10.1038/nature13453

July 1, 2014
A Magic Trick of Telomerase Revealed

Each time before a cell divides, DNA polymerases must make a copy of the genome. Similar to a typewriter, DNA polymerases type out the entire DNA sequence faithfully from the given parental script, without needing to understand the text.

Telomerase is a one-of-a-kind DNA polymerase with its own innate transcript for making DNA repeats at the ends of chromosomes within our cells. This special task of telomerase is intimately associated with human ageing, as the accelerated loss of DNA sequences from the ends of the genome results in genome instability, disease, infertility, and death.
Telomerase is distinguished from all known DNA polymerases by working as an intelligent typewriting enzyme. More specifically, this enzyme has the unparalleled talent to interpret the meaning of its script for synthesizing the intended DNA repeats. Researchers led by Prof. Julian J.-L. Chen at Arizona State University found that telomerase uses a previously unidentified signal embedded within the script itself to specify the precise phrase 'GGTTAG',. This unique ability is imperative for telomerase to magically type out many copies of the exact sequence GGTTAG through a repeated cycle. It is vitally important that telomerase types this exact phrase. An incomplete or incorrect phrase, by even a single letter, would not be understood by the cell and would damage it.

As Dr. Chen explains, “The message written by telomerase is read by additional proteins within the cell and thus must be accurately and precisely generated. Even the smallest change in the message would result in miscommunication with these critical proteins that protect our chromosomes, and would be extremely detrimental to the wellbeing of the cell.” These findings, published this week in the journal Proceeding of the National Academy of Sciences, finally answer how human telomerase can reliably read its script so as to accurately and precisely type out the correct message to safeguard our genome.
This work was supported by the National Institutes of Health (NIH) (R01GM094450 to J.J.-L.C.) with the goal of fundamentally understanding telomerase for the future development of therapeutics against cancer, ageing, and disease.

"A self-regulating template in human telomerase", Brown, A.F., J.D. Podlevsky, X. Qi, Y. Chen, M. Xie, and J.J.-L. Chen, Proc. Natl. Acad. Sci. U.S.A. (2014) doi:10.1073/pnas.1402531111 (published online June 30th, 2014)

Source: Joshua Podlevsky, (480) 965-1928;
Media contact: Jenny Green, (480) 965-1430;

May 4, 2014
ASU, Chinese scientists unlock secrets of the fountain of youth

Telomerase is a large ribonucleoprotein complex minimally composed of a catalytic telomerase reverse transcriptase (TERT) and an RNA component (TR) that provides the template for telomeric DNA synthesis. However, it remains unclear how TERT and TR assemble into a functional telomerase. Here we report the crystal structure of the conserved regions 4 and 5 (CR4/5) of TR in complex with the TR-binding domain (TRBD) of TERT from the teleost fish Oryzias latipes. The structure shows that CR4/5 adopts an L-shaped three-way-junction conformation with its two arms clamping onto TRBD. Both the sequence and conformation of CR4/5 are required for the interaction. Our structural and mutational analyses suggest that the observed CR4/5-TRBD recognition is common to most eukaryotes, and CR4/5 in vertebrate TR might have a similar role in telomerase regulation as that of stem-loop IV in Tetrahymena TR.

"Structural basis for protein-RNA recognition in telomerase", Jing Huang, Andrew F Brown, Jian Wu, Jing Xue, Christopher J Bley, Dustin P Rand, Lijie Wu, Rongguang Zhang, Julian J-L Chen & Ming Lei, Nature Structural & Molecular Biology (2014) doi:10.1038/nsmb.2819

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February 9 2014
A bioinspired redox relay that mimics radical interactions of the Tyr - His pairs of photosystem II

"A bioinspired redox relay that mimics radical interactions of the Tyr - His pairs of photosystem II", Jackson D. Megiatto Jr, Dalvin D. Mendez-Hernandez, Marely E. Tejeda-Ferrari, Anne-Lucie Teillout, Manuel J. Llansola-Portoles, Gerdenis Kodis, Oleg G. Poluektov, Tijana Rajh, Vladimiro Mujica, Thomas L. Groy, Devens Gust, Thomas A. Moore & Ana L. Moore, Nature Chemistry (2014) doi:10.1038/nchem.1862 Published online 09 February 2014

In water-oxidizing photosynthetic organisms, light absorption generates a powerfully oxidizing chlorophyll complex (P680•+) in the photosystem II reaction centre. This is reduced via an electron transfer pathway from the manganese-containing water-oxidizing catalyst, which includes an electron transfer relay comprising a tyrosine (Tyr)–histidine (His) pair that features a hydrogen bond between a phenol group and an imidazole group. By rapidly reducing P680•+, the relay is thought to mitigate recombination reactions, thereby ensuring a high quantum yield of water oxidation. Here, we show that an artificial reaction centre that features a benzimidazole–phenol model of the Tyr–His pair mimics both the short-internal hydrogen bond in photosystem II and, using electron paramagnetic resonance spectroscopy, the thermal relaxation that accompanies proton-coupled electron transfer. Although this artificial system is much less complex than the natural one, theory suggests that it captures the essential features that are important in the function of the relay.

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September 4, 2013
Dielectrophoretic Sorting of Membrane Protein Nanocrystals

"Dielectrophoretic Sorting of Membrane Protein Nanocrystals", Bahige G. Abdallah , Tzu-Chiao Chao, Christopher Kupitz, Petra Fromme, and Alexandra Ros, ACS Nano, 2013, 7 (10), pp 9129–9137
DOI: 10.1021/nn403760q

Structure elucidation of large membrane protein complexes is still a considerable challenge, yet is a key factor in drug development and disease combat. Femtosecond nanocrystallography is an emerging technique with which structural information of membrane proteins is obtained without the need to grow large crystals, thus overcoming the experimental riddle faced in traditional crystallography methods. Here, we demonstrate for the first time a microfluidic device capable of sorting membrane protein crystals based on size using dielectrophoresis. We demonstrate the excellent sorting power of this new approach with numerical simulations of selected submicrometer beads in excellent agreement with experimental observations. Crystals from batch crystallization broths of the huge membrane protein complex photosystem I were sorted without further treatment, resulting in a high degree of monodispersity and crystallinity in the 100 nm size range. Microfluidic integration, continuous sorting, and nanometer-sized crystal fractions make this method ideal for direct coupling to femtosecond nanocrystallography.

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August 12, 2013
Bacterial photosynthesis is optimized and controlled by tuning time-scales of protein relaxation to rates of electron transfer

"Protein dynamics to optimize and control bacterial photosynthesis",  David N. LeBard, Daniel R. Martin,  Su Lin,  Neal W. Woodbury and Dmitry V. Matyushov, Chem. Sci., 2013, 4, 4127-4136, DOI: 10.1039/C3SC51327K

Proteins function by sampling conformational sub-states within a given fold. How this configurational flexibility and the associated protein dynamics affect the rates of chemical reactions are open questions. The difficulty in exploring this issue arises in part from the need to identify the relevant nuclear modes affecting the reaction rate for each characteristic time-scale of the reaction. Proteins as reaction media display a hierarchy of such nuclear modes, of increasingly collective character, that produce both a broad spectrum of static fluctuations and a broad spectrum of relaxation times. In order to understand the effect of protein dynamics on reaction rates, we have chosen to study a sub-nanosecond electron transfer reaction between the bacteriopheophytin and primary quinone cofactors of the photosynthetic bacterial reaction center. We show that dynamics affects the activation barrier of the reaction through a dynamical restriction of the configurational space sampled by the protein–water solvent on the reaction time-scale. The modes which become dynamically arrested on the reaction time-scale of hundreds of picoseconds are related to elastic motions of the protein that are strongly coupled to the hydration layer of water. Several mechanistic consequences for protein electron transfer emerge from this picture. Importantly, energy parameters used to define the activation barrier of electron transfer reactions lose their direct connection to equilibrium thermodynamics and become dependent in a very direct way on the relative magnitudes of the reaction and nuclear reorganization time-scales. As a result, the energetics of protein electron transfer need to be defined on each specific reaction time-scale. This perspective offers a mechanism to optimize protein electron transfer by tuning the reaction rate to the relaxation spectrum of the reaction coordinate.

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August 30, 2013
"Miracle materials" - metal-Organic Frameworks

"The Chemistry and Applications of Metal-Organic Frameworks", Hiroyasu Furukawa, Kyle E. Cordova, Michael O’Keeffe, Omar M.Yaghi, Science 30 August 2013: Vol. 341 no. 6149 DOI: 10.1126/science.1230444

Crystalline metal-organic frameworks (MOFs) are formed by reticular synthesis, which creates strong bonds between inorganic and organic units. Careful selection of MOF constituents can yield crystals of ultrahigh porosity and high thermal and chemical stability. These characteristics allow the interior of MOFs to be chemically altered for use in gas separation, gas storage, and catalysis, among other applications. The precision commonly exercised in their chemical modification and the ability to expand their metrics without changing the underlying topology have not been achieved with other solids. MOFs whose chemical composition and shape of building units can be multiply varied within a particular structure already exist and may lead to materials that offer a synergistic combination of properties.

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August 8, 2013
Carbon under pressure exhibits some interesting traits

"Carbon storage at defect sites in mantle mineral analogues", Jun Wu, Peter R. Buseck, Nature Geoscience (2013) doi:10.1038/ngeo190

A significant fraction of Earth’s carbon resides in the mantle, but the mode of carbon storage presents a long-standing problem. The mantle contains fluids rich in carbon dioxide and methane, carbonate-bearing melts, carbonate minerals, graphite, diamond and carbides, as well as dissolved carbon atoms in metals. However, it is uncertain whether these can sufficiently account for the total amount of carbon thought to be stored in the mantle and the volume of carbon degassed from the mantle at volcanoes. Moreover, such carbon hosts should significantly affect the physical and chemical behaviour of the mantle, including its melting temperature, electrical conductivity and oxidation state. Here we use in situ transmission electron microscopy to measure the storage of carbon within common mantle mineral analogues--nickel-doped lanthanum chromate perovskite and titanium dioxide--in laboratory experiments at high pressure and temperature. We detect elevated carbon concentrations at defect sites in the nanocrystals, maintained at high pressures within annealed carbon nanocages. Specifically, our experiments show that small stacking faults within the mantle analogue materials are effective carbon sinks at mantle conditions, potentially providing an efficient mechanism for carbon storage in the mantle. Furthermore, this carbon can be readily released under lower pressure conditions, and may therefore help to explain carbon release in volcanic eruptions.

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July 3, 2013
A DNA tweezer-actuated enzyme nanoreactor

"A DNA Tweezer-actuated Enzyme Nanoreactor," Liu, Minghui, Jinglin Fu, Christian Hejesen, Yuhe Yang, Neal W. Woodbury, Kurt Gothelf, Yan Liu, and Hao Yan. Nature 4 (2013) doi:10.1038/ncomms3127

The functions of regulatory enzymes are essential to modulating cellular pathways. Here we report a tweezer-like DNA nanodevice to actuate the activity of an enzyme/cofactor pair. A dehydrogenase and NAD+ cofactor are attached to different arms of the DNA tweezer structure and actuation of enzymatic function is achieved by switching the tweezers between open and closed states. The enzyme/cofactor pair is spatially separated in the open state with inhibited enzyme function, whereas in the closed state, enzyme is activated by the close proximity of the two molecules. The conformational state of the DNA tweezer is controlled by the addition of specific oligonucleotides that serve as the thermodynamic driver (fuel) to trigger the change. Using this approach, several cycles of externally controlled enzyme inhibition and activation are successfully demonstrated. This principle of responsive enzyme nanodevices may be used to regulate other types of enzymes and to introduce feedback or feed-forward control loops.

Figure 1 Enzyme Nanotweezers
Left panel shows tweezers in the open position, with the enzyme (green) on
the upper arm and the co-factor (gold) on the lower arm.

Supplying a complementary fuel strand causes the tweezers to close, producing the reaction of the enzyme-cofactor pair. (Right panel) while a set strand restores the tweezers to their open position

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March 8, 2013
Watching’ Hydrogen Bonded Structures in an Alcohol Convert from Rings to Chains

"Watching’ Hydrogen Bonded Structures in an Alcohol Convert from Rings to Chains", Singh, Lokendra; Richert, Ranko, Physical Review Letters, Volume 109, issue 16 (October 19, 2012), p. 167802 - 167806. ISSN: 0031-9007 DOI: 10.1103/PhysRevLett.109.167802

In hydrogen-bonded liquids including monohydroxy alcohols, the prominent Debye process that often dominates the dielectric relaxation behavior is associated with hydrogen bonding, but its microscopic origin has remained unclear to date. High electric field impedance spectroscopy on 5-methyl-3-heptanol reveals a field-induced change in the Kirkwood-Frohlich correlation factor gK, viewed as evidence for an electric field driven conversion from ring- to chain-type hydrogen-bonded structures. The concomitant rearrangement of the chain structure is observed to occur on the time scale of the Debye process, suggesting that the Debye peak of monohydroxy alcohols originates from a fluctuation of the net dipole moment via gK of the chain structures on a time scale that is largely controlled by viscosity.

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Nov 9, 2012
Hydrogenase mimics for solar fuel production

Photo-induced hydrogen production in a helical peptide incorporating a [FeFe] hydrogenase active site mimic”, Roy A., Madden C., and Ghirlanda G. Chemical Communications (2012) 48, 9816-18

There is growing interest in the development of hydrogenase mimics for solar fuel production. Here, we present a bioinspired mimic designed by anchoring a diiron hexacarbonyl cluster to a model helical peptide via an artificial dithiol amino acid. The [FeFe]-peptide complex catalyses photo-induced production of hydrogen in water.

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August 10, 2012
Pizzarello: Antarctic meteorites and cosmochemical evolution

"Large enantiomeric excesses in primitive meteorites and the diverse effects of water in cosmochemical evolution", Pizzarello S., Schrader D.L., Monroe A.A. and Lauretta D.S. PNAS (2012).

Carbonaceous chondrites are meteoritic fragments of asteroids that avoided the geological reprocessing of larger planets and allow laboratory probing of early solar-nebula materials. Among these, Renazzo-type (CR) chondrites found in Antarctica appear remarkably pristine and are distinguished by abundant organic materials and water-soluble molecules such as amino acids and ammonia. We present a comprehensive analysis of the organic composition of selected CR meteorites of different petrographic classification and compare compounds' abundance and distribution as they may relate to asteroidal aqueous processing and concomitant evolution of the mineral phases. We found that several CR compounds such as amino acids and sugar alcohols are fully represented in stones with no or minimal water exposure indicating a formation that, if solar, preceded parent body processes. The most pristine CRs also revealed natal enantiomeric excesses (ee) of up to 60%, much larger than ever recorded. However, aqueous alteration appears to affect CR soluble organic composition and abundances, in particular some diastereomeric amino acids may gauge its extent by the consequent racemization of their ee.

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May 15, 2012
Untangling mysteries of spider silk

"Total X-Ray Scattering of Spider Dragline Silk", C. J. Benmore, T. Izdebski, and J. L. Yarger Phys. Rev. Lett. 108, 178102 (2012) – Published April 24, 2012

Total x-ray scattering measurements of spider dragline silk fibers from Nephila clavipes, Argiope aurantia, and Latrodectus hesperus all yield similar structure factors, with only small variations between the different species. Wide-angle x-ray scattering from fibers orientated perpendicular to the beam shows a high degree of anisotropy, and differential pair distribution functions obtained by integrating over wedges of the equatorial and meridian planes indicate that, on average, the majority (95%) of the atom-atom correlations do not extend beyond 1 nm. Futhermore, the atom-atom correlations between 1 and 3 nm are not associated with the most intense diffraction peaks at Q=1-2 A-1. Disordered molecular orientations along the fiber axis are consistent with proteins in similar structural arrangements to those in the equatorial plane, which may be associated with the silk’s greater flexibility in this direction.

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April 18, 2012
Hayes & Herckes explore novel fingerprinting technique

"Exploring the feasibility of bioaerosol analysis as a novel fingerprinting technique", Josemar A. Castillo, Sarah J. R. Staton, Thomas J. Taylor, Pierre Herckes and Mark A. Hayes, Anal Bioanal Chem, 2012, 403(1), 15-26, DOI: 10.1007/s00216-012-5725-0

The purpose of this review is to investigate the feasibility of bioaerosol fingerprinting based on current understanding of cellular debris (with emphasis on human-emitted particulates) in aerosols and arguments regarding sampling, sensitivity, separations, and detection schemes. Target aerosol particles include cellular material and proteins emitted by humans, animals, and plants and can be regarded as information-rich packets that carry biochemical information specific to the living organisms present where the sample is collected. In this work we discuss sampling and analysis techniques that can be integrated with molecular (e.g. protein)-detection procedures to properly assess the aerosolized cellular material of interest. Developing a detailed understanding of bioaerosol molecular profiles in different environments suggests exciting possibilities of bioaerosol analysis with applications ranging from military defense to medical diagnosis and wildlife identification.

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One of the outstanding questions of early Earth biology is how ancient organisms made the evolutionary transition from anoxygenic (no oxygen produced) to oxygenic (oxygen-producing) photosynthesis. A team of scientists from ASU has moved us significantly closer to understanding this problem. Photo by: stock.xchng

April 5, 2012
Allen and Williams shine new light on photosynthesis

"Light-driven oxygen production from superoxide by Mn-binding bacterial reaction centers", James P. Allen, Tien L. Olson, Paul Oyala, Wei-Jen Lee, Aaron A. Tufts, and JoAnn C. Williams, Proceedings of the National Academy of Sciences, (2012) Volume 109, pages 2314-2318

One of the outstanding questions concerning the early Earth is how ancient phototrophs made the evolutionary transition from anoxygenic to oxygenic photosynthesis, which resulted in a substantial increase in the amount of oxygen in the atmosphere. We have previously demonstrated that reaction centers from anoxygenic photosynthetic bacteria can be modified to bind a redox-active Mn cofactor, thus gaining a key functional feature of photosystem II, which contains the site for water oxidation in cyanobacteria, algae, and plants [Thielges M, et al. (2005) Biochemistry 44:7389-7394]. In this paper, the Mn-binding reaction centers are shown to have a light-driven enzymatic function; namely, the ability to convert superoxide into molecular oxygen. This activity has a relatively high efficiency with a k cat of approximately 1 s-1 that is significantly larger than typically observed for designed enzymes, and a K m of 35-40 micrometers that is comparable to the value of 50 micrometers for Mn-superoxide dismutase, which catalyzes a similar reaction. Unlike wild-type reaction centers, the highly oxidizing reaction centers are not stable in the light unless they have a bound Mn. The stability and enzymatic ability of this type of Mn-binding reaction centers would have provided primitive phototrophs with an environmental advantage before the evolution of organisms with a more complex Mn4Ca cluster needed to perform the multielectron reactions required to oxidize water.

Jenny Green,
School of Molecular Sciences

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March 12, 2012
What ruled the world before DNA and RNA?

"Darwinian evolution of an alternative genetic system provides support for TNA as an RNA progenitor", Hanyang Yu, Su Zhan and John C.Chaput, Nature Chemistry (2012) doi:10.1038/nchem.1241.

The pre-RNA world hypothesis postulates that RNA was preceded in the evolution of life by a simpler genetic material, but it is not known if such systems can fold into structures capable of eliciting a desired function. Presumably, whatever chemistry gave rise to RNA would have produced other RNA analogues, some of which may have preceded or competed directly with RNA. Threose nucleic acid (TNA), a potentially natural derivative of RNA, has received considerable interest as a possible RNA progenitor due to its chemical simplicity and ability to exchange genetic information with itself and RNA. Here, we have applied Darwinian evolution methods to evolve, in vitro, a TNA receptor that binds to an arbitrary target with high affinity and specificity. This demonstration shows that TNA has the ability to fold into tertiary structures with sophisticated chemical functions, which provides evidence that TNA could have served as an ancestral genetic system during an early stage of life.

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October 10, 2011
New technique unlocks secrets of ancient ocean

"Rapid expansion of oceanic anoxia immediately before the end-Permian mass extinction", Gregory A. Brenneckaa, Achim D. Herrmanna,Thomas J. Algeoc, and Ariel D. Anbar, Published online before print October 10, 2011, doi: 10.1073/pnas.1106039108 PNAS October 10, 2011

Periods of oceanic anoxia have had a major influence on the evolutionary history of Earth and are often contemporaneous with mass extinction events. Changes in global (as opposed to local) redox conditions can be potentially evaluated using U system proxies. The intensity and timing of oceanic redox changes associated with the end-Permian extinction horizon (EH) were assessed from variations in 238U/235U (g238U) and Th/U ratios in a carbonate section at Dawen in southern China. The EH is characterized by shifts toward lower g238U values (from -0.37% to -0.65%), indicative of an expansion of oceanic anoxia, and higher Th/U ratios (from 0.06 to 0.42), indicative of drawdown of U concentrations in seawater. Using a mass balance model, we estimate that this isotopic shift represents a sixfold increase in the flux of U to anoxic facies, implying a corresponding increase in the extent of oceanic anoxia. The intensification of oceanic anoxia coincided with, or slightly preceded, the EH and persisted for an interval of at least 40,000 to 50,000 y following the EH. These findings challenge previous hypotheses of an extended period of whole-ocean anoxia prior to the end-Permian extinction.

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August 30, 2011
Light Harvesting Antennas - Holding on to DNA

"Holding on to DNA", Anne Pichon Nature Chemistry 3, 654 (2011) doi:10.1038/nchem.1134, Published online 23 August 2011  

Using the energy of visible light to fuel chemical conversions in a similar manner to photosynthesis is extremely attractive. Multiple chromophore systems, attached to dendrimers or protein assemblies, have been constructed that are able to capture light and transport the excitation energy in one direction through donor-acceptor energy-transfer processes, but organizing a large number of multiple chromophores with precision remains challenging.

Yan Liu and co-workers from Arizona State University have now used a DNA scaffold to prepare rapid and efficient light-harvesting antennas. A seven-helix DNA bundle, in which six helices surround a protruding one, holds cyclic arrays of three chromophores attached to the DNA fairly rigidly - either through a base or directly incorporated into the backbone - at well-controlled inter-chromophore distances. They are arranged to favour a stepwise energy transfer from the primary donor to the intermediate donor, then to the acceptor at the protruding site.

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Structural overlay of the activase C-domain(yellow) onto the hexameric assembly of FtsH, a remote homolog (blue)

September 14, 2011
How do higher plants regulate CO 2 assimilation under heat-stress conditions?

"Atomic resolution X-ray structure of the substrate recognition domain of higher plant Rubisco activase", J. Nathan Henderson, Agnieszka M. Kuriata, Raimund Fromme, Michael E. Salvucci and Rebekka M. Wachter, JBC, 2011, doi: 10.1074/jbc.C111.289595

The rapid release of tight-binding inhibitors from dead-end ribulose-bisphosphate carboxylase/oxygenase (Rubisco) complexes requires the activity of Rubisco activase, an AAA+ ATPase that utilizes chemo-mechanical energy to catalyze the reactivation of Rubisco. Activase is thought to play a central role in coordinating the rate of CO(2) fixation with the light reactions of photosynthesis. Here, we present a 1.9 Å crystal structure of the C-domain core of creosote activase. The fold consists of a canonical four-helix bundle, from which a paddle-like extension protrudes that entails a nine-turn helix lined by an irregularly structured peptide strand. The residues Lys-313 and Val-316 involved in the species-specific recognition of Rubisco are located near the tip of the paddle. An ionic bond between Lys-313 and Glu-309 appears to stabilize the glycine-rich end of the helix. Structural superpositions onto the distant homolog FtsH imply that the paddles extend away from the hexameric toroid in a fan-like fashion, such that the hydrophobic sides of each blade bearing Trp-302 are facing inward and the polar sides bearing Lys-313 and Val-316 are facing outward. Therefore, we speculate that upon binding, the activase paddles embrace the Rubisco cylinder by placing their hydrophobic patches near the partner protein. This model suggests that conformational adjustments at the remote end of the paddle may relate to selectivity in recognition, rather than specific ionic contacts involving Lys-313. Additionally, the superpositions predict that the catalytically critical Arg-293 does not interact with the bound nucleotide. Hypothetical ring-ring stacking and peptide threading models for Rubisco reactivation are briefly discussed.

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August 31, 2011
Molecules as mini-computers

"All-Photonic Multifunctional Molecular Logic Device",  oakim Andrasson, Uwe Pischel, Stephen D. Straight Thomas A. Moore, Ana L. Moore, and Devens Gust, JACS, August 3, 201, Volume 133, Issue 30 Pages 11641-11648.

Photochromes are photoswitchable, bistable chromophores which, like transistors, can implement binary logic operations. When several photochromes are combined in one molecule, interactions between them such as energy and electron transfer allow design of simple Boolean logic gates and more complex logic devices with all-photonic inputs and outputs. Selective isomerization of individual photochromes can be achieved using light of different wavelengths, and logic outputs can employ absorption and emission properties at different wavelengths, thus allowing a single molecular species to perform several different functions, even simultaneously. Here, we report a molecule consisting of three linked photochromes that can be configured as AND, XOR, INH, half-adder, half-subtractor, multiplexer, demultiplexer, encoder, decoder, keypad lock, and logically reversible transfer gate logic devices, all with a common initial state. The system demonstrates the advantages of light-responsive molecules as multifunctional, reconfigurable nanoscale logic devices that represent an approach to true molecular information processing units.

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June 6, 2011

"Dynamics of Nucleosome Invasion by DNA Binding Proteins", Hannah S. Tims , Kaushik Gurunathan, Marcia Levitus, Jonathan Widom, J. Mol. Biol. (2011) 411, 430–448.

Nucleosomes sterically occlude their wrapped DNA from interacting with many large protein complexes. How proteins gain access to nucleosomal DNA target sites in vivo is not known. Outer stretches of nucleosomal DNA spontaneously unwrap and rewrap with high frequency, providing rapid and efficient access to regulatory DNA target sites located there; however, rates for access to the nucleosome interior have not been measured. Here we show that for a selected high-affinity nucleosome positioning sequence, the spontaneous DNA unwrapping rate decreases dramatically with distance inside the nucleosome. The rewrapping rate also decreases, but only slightly. Our results explain the previously known strong position dependence on the equilibrium accessibility of nucleosomal DNA, which is characteristic of both selected and natural sequences. Our results point to slow nucleosome conformational fluctuations as a potential source of cell-cell variability in gene activation dynamics, and they reveal the dominant kinetic path by which multiple DNA binding proteins cooperatively invade a nucleosome.

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August 23, 2011
Peptide-Modified Surfaces for Enzyme Immobilization
Jinglin Fu, Jeremy Reinhold and Neal W. Woodbury

"Peptide-Modified Surfaces for Enzyme Immobilization.", Fu J, Reinhold J, Woodbury NW, PLoS ONE 6(4):e18692 (2011). doi: 10.1371 / journal.pone. 0018692

Chemistry and particularly enzymology at surfaces is a topic of rapidly growing interest, both in terms of its role in biological systems and its application in biocatalysis. Existing protein immobilization approaches, including noncovalent or covalent attachments to solid supports, have difficulties in controlling protein orientation, reducing nonspecific absorption and preventing protein denaturation. New strategies for enzyme immobilization are needed that allow the precise control over orientation and position and thereby provide optimized activity.

A method is presented for utilizing peptide ligands to immobilize enzymes on surfaces with improved enzyme activity and stability. The appropriate peptide ligands have been rapidly selected from high-density arrays and when desirable, the peptide sequences were further optimized by single-point variant screening to enhance both the affinity and activity of the bound enzyme. For proof of concept, the peptides that bound to β-galactosidase and optimized its activity were covalently attached to surfaces for the purpose of capturing target enzymes. Compared to conventional methods, enzymes immobilized on peptide-modified surfaces exhibited higher specific activity and stability, as well as controlled protein orientation.

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