A combined biophysical approach was applied to map gas-docking sites within murine neuroglobin (Ngb), revealing snapshots of events that might govern activity and dynamics in this unique hexacoordinate globin, which is most likely to be involved in gas-sensing in the central nervous system and for which a precise mechanism of action remains to be elucidated. The application of UV–visible microspectroscopy in crystallo, solution X-ray absorption near-edge spectroscopy and X-ray diffraction experiments at 15–40 K provided the structural characterization of an Ngb photolytic intermediate by cryo-trapping and allowed direct observation of the relocation of carbon monoxide within the distal heme pocket after photodissociation. Moreover, X-ray diffraction at 100 K under a high pressure of dioxygen, a physiological ligand of Ngb, unravelled the existence of a storage site for O2 in Ngb which coincides with Xe-III, a previously described docking site for xenon or krypton. Notably, no other secondary sites were observed under our experimental conditions.

Copper-containing nitrite reductases (CuNiRs) that convert NO2− to NO via a CuCAT–His–Cys–CuET proton-coupled redox system are of central importance in nitrogen-based energy metabolism. These metalloenzymes, like all redox enzymes, are very susceptible to radiation damage from the intense synchrotron-radiation X-rays that are used to obtain structures at high resolution. Understanding the chemistry that underpins the enzyme mechanisms in these systems requires resolutions of better than 2 Å. Here, for the first time, the damage-free structure of the resting state of one of the most studied CuNiRs was obtained by combining X-ray free-electron laser (XFEL) and neutron crystallography. This represents the first direct comparison of neutron and XFEL structural data for any protein. In addition, damage-free structures of the reduced and nitrite-bound forms have been obtained to high resolution from cryogenically maintained crystals by XFEL crystallography. It is demonstrated that AspCAT and HisCAT are deprotonated in the resting state of CuNiRs at pH values close to the optimum for activity. A bridging neutral water (D2O) is positioned with one deuteron directed towards AspCAT Oδ1 and one towards HisCAT N∊2. The catalytic T2Cu-ligated water (W1) can clearly be modelled as a neutral D2O molecule as opposed to D3O+ or OD−, which have previously been suggested as possible alternatives. The bridging water restricts the movement of the unprotonated AspCAT and is too distant to form a hydrogen bond to the O atom of the bound nitrite that interacts with AspCAT. Upon the binding of NO2− a proton is transferred from the bridging water to the Oδ2 atom of AspCAT, prompting electron transfer from T1Cu to T2Cu and reducing the catalytic redox centre. This triggers the transfer of a proton from AspCAT to the bound nitrite, enabling the reaction to proceed.

The interoperability of chemical and biological crystallographic data is a key challenge to research and its application to pharmaceutical design. Research attempting to combine data from the two disciplines, small-molecule or chemical crystallography (CX) and macromolecular crystallography (MX), will face unique challenges including variations in terminology, software development, file format and databases which differ significantly from CX to MX. This perspective overview spans the two disciplines and originated from the investigation of protein binding to model radiopharmaceuticals. The opportunities of interlinked research while utilizing the two databases of the CSD (Cambridge Structural Database) and the PDB (Protein Data Bank) will be highlighted. The advantages of software that can handle multiple file formats and the circuitous route to convert organometallic small-molecule structural data for use in protein refinement software will be discussed. In addition some pointers to avoid being shipwrecked will be shared, such as the care which must be taken when interpreting data precision involving small molecules versus proteins.

High-throughput X-ray crystal structures of protein–ligand complexes are critical to pharmaceutical drug development. However, cryocooling of crystals and X-ray radiation damage may distort the observed ligand binding. Serial femtosecond crystallography (SFX) using X-ray free-electron lasers (XFELs) can produce radiation-damage-free room-temperature structures. Ligand-binding studies using SFX have received only modest attention, partly owing to limited beamtime availability and the large quantity of sample that is required per structure determination. Here, a high-throughput approach to determine room-temperature damage-free structures with excellent sample and time efficiency is demonstrated, allowing complexes to be characterized rapidly and without prohibitive sample requirements. This yields high-quality difference density maps allowing unambiguous ligand placement. Crucially, it is demonstrated that ligands similar in size or smaller than those used in fragment-based drug design may be clearly identified in data sets obtained from <1000 diffraction images. This efficiency in both sample and XFEL beamtime opens the door to true high-throughput screening of protein–ligand complexes using SFX.

The disposition of functional groups can induce variations in the nature and type of interactions and hence affect the molecular recognition and self-assembly mechanism in cocrystals. To better understand the formation of cocrystals on a molecular level, the effects of disposition of functional groups on the formation of cocrystals were systematically and comprehensively investigated using cresol isomers (o-, m-, p-cresol) as model compounds. Consistency and variability in these cocrystals containing positional isomers were found and analyzed. The structures, molecular recognition and self-assembly mechanism of supramolecular synthons in solution and in their corresponding cocrystals were verified by a combined experimental and theoretical calculation approach. It was found that the heterosynthons (heterotrimer or heterodimer) combined with O—H⋯N hydrogen bonding played a significant role. Hirshfeld surface analysis and computed interaction energy values were used to determine the hierarchical ordering of the weak interactions. The quantitative analyses of charge transfers and molecular electrostatic potential were also applied to reveal and verify the reasons for consistency and variability. Finally, the molecular recognition, self-assembly and evolution process of the supramolecular synthons in solution were investigated. The results confirm that the supramolecular synthon structures formed initially in solution would be carried over to the final cocrystals, and the supramolecular synthon structures are the precursors of cocrystals and the information memory of the cocrystallization process, which is evidence for classical nucleation theory.

The application of thermoelectrics for energy harvesting depends strongly on operational reliability and it is therefore desirable to investigate the structural integrity of materials under operating conditions. We have developed an operando setup capable of simultaneously measuring X-ray scattering data and electrical resistance on pellets subjected to electrical current. Here, operando investigations of β-Zn4Sb3 are reported at current densities of 0.5, 1.14 and 2.3 A mm−2. At 0.5 A mm−2 no sample decomposition is observed, but Rietveld refinements reveal increased zinc occupancy from the anode to the cathode demonstrating zinc migration under applied current. At 1.14 A mm−2 β-Zn4Sb3 decomposes into ZnSb, but pair distribution function analysis shows that Zn2Sb2 units are preserved during the decomposition. This identifies the mobile zinc in β-Zn4Sb3 as the linkers between the Zn2Sb2 units. At 2.3 A mm−2 severe Joule heating triggers transition into the γ-Zn4Sb3 phase, which eventually decomposes into ZnSb, demonstrating Zn ion mobility also in γ-Zn4Sb3 under electrical current.

During single-crystal-to-single-crystal (SCSC) phase transitions, a polymorph of a compound can transform to a more stable form while remaining in the solid state. By understanding the mechanism of these transitions, strategies can be developed to control this phenomenon. This is particularly important in the pharmaceutical industry, but also relevant for other industries such as the food and agrochemical industries. Although extensive literature exists on SCSC phase transitions in inorganic crystals, it is unclear whether their classications and mechanisms translate to molecular crystals, with weaker interactions and more steric hindrance. A comparitive study of SCSC phase transitions in aliphatic linear-chain amino acid crystals, both racemates and quasi-racemates, is presented. A total of 34 transitions are considered and most are classified according to their structural change during the transition. Transitions without torsional changes show very different characteristics, such as transition temperature, enthalpy and free energy, compared with transitions that involve torsional changes. These differences can be rationalized using classical nucleation theory and in terms of a difference in mechanism; torsional changes occur in a molecule-by-molecule fashion, whereas transitions without torsional changes involve cooperative motion with multiple molecules at the same time.

The three probes of the structure of matter (X-rays, neutrons and electrons) in biology have complementary properties and strengths. The balance between these three probes within their strengths and weaknesses is perceived to change, even dramatically so at times. For the study of combined states of order and disorder, NMR crystallography is also applicable. Of course, to understand biological systems the required perspectives are surely physiologically relevant temperatures and relevant chemical conditions, as well as a minimal perturbation owing to the needs of the probe itself. These remain very tough challenges because, for example, cryoEM by its very nature will never be performed at room temperature, crystallization often requires nonphysiological chemical conditions, and X-rays and electrons cause beam damage. However, integrated structural biology techniques and functional assays provide a package towards physiological relevance of any given study. Reporting of protein crystal structures, and their associated database entries, could usefully indicate how close to the biological situation they are, as discussed in detail in this feature article.

The phase transition of E-vanillyl oxime {1-[(E)-(hydroxyimino)methyl]-4-hydroxy-3-methoxybenzene, C8H9NO3} has been analysed by single-crystal and powder X-ray diffraction. The high-temperature (HT) phase (P21/a, Z' = 1) transforms into the low-temperature (LT) phase (threefold superstructure, Poverline{1}, Z' = 6) at ca 190 K. The point operations lost on cooling, {m[010], 2[010]}, are retained as twin operations and constitute the twin law. The screw rotations and glide reflections are retained in the LT phase as partial operations acting on a subset of Euclidean space {b E}^3. The full symmetry of the LT phase, including partial operations, is described by a disconnected space groupoid which is built of three connected components.

This paper discusses the full structural solution of the hybrid perovskite formamidinium lead tribromide (FAPbBr3) and its temperature-dependent phase transitions in the range from 3 K to 300 K using neutron powder diffraction and synchrotron X-ray diffraction. Special emphasis is put on the influence of deuteration on formamidinium, its position in the unit cell and disordering in comparison to fully hydrogenated FAPbBr3. The temperature-dependent measurements show that deuteration critically influences the crystal structures, i.e. results in partially-ordered temperature-dependent structural modifications in which two symmetry-independent molecule positions with additional dislocation of the molecular centre atom and molecular angle inclinations are present.

The room-temperature experiment has been revisited for macromolecular crystallography. Despite being limited by radiation damage, such experiments reveal structural differences depending on temperature, and it is expected that they will be able to probe structures that are physiologically alive. For such experiments, the humid-air and glue-coating (HAG) method for humidity-controlled experiments is proposed. The HAG method improves the stability of most crystals in capillary-free experiments and is applicable at both cryogenic and ambient temperatures. To expand the thermal versatility of the HAG method, a new humidifier and a protein-crystal-handling workbench have been developed. The devices provide temperatures down to 4°C and successfully maintain growth at that temperature of bovine cytochrome c oxidase crystals, which are highly sensitive to temperature variation. Hence, the humidifier and protein-crystal-handling workbench have proved useful for temperature-sensitive samples and will help reveal temperature-dependent variations in protein structures.

Small-angle neutron scattering (SANS) was recently applied to the in situ and operando study of the charge/discharge process in Li-ion battery full-cells based on a pouch cell design. Here, this work is continued in a half-cell with a graphite electrode cycled versus a metallic lithium counter electrode, in a study conducted on the SANS-1 instrument of the neutron source FRM II at the Heinz Maier-Leibnitz Zentrum in Garching, Germany. It is confirmed that the SANS integrated intensity signal varies as a function of graphite lithiation, and this variation can be explained by changes in the squared difference in scattering length density between graphite and the electrolyte. The scattering contrast change upon graphite lithiation/delithiation calculated from a multi-phase neutron scattering model is in good agreement with the experimentally measured values. Due to the finite coherence length, the observed SANS contrast, which mostly stems from scattering between the (lithiated) graphite and the electrolyte phase, contains local information on the mesoscopic scale, which allows the development of lithiated phases in the graphite to be followed. The shape of the SANS signal curve can be explained by a core–shell model with step-wise (de)lithiation from the surface. Here, for the first time, X-ray diffraction, SANS and theory are combined to give a full picture of graphite lithiation in a half-cell. The goal of this contribution is to confirm the correlation between the integrated SANS data obtained during operando measurements of an Li-ion half-cell and the electrochemical processes of lithiation/delithiation in micro-scaled graphite particles. For a deeper understanding of this correlation, modelling and experimental data for SANS and results from X-ray diffraction were taken into account.

A new temperature-controllable humidifier for X-ray diffraction has been developed. It is shown that the humidifier can successfully maintain protein crystal growth at a temperature lower than room temperature.

This article describes rational strategies for the optimization of crystal growth using precise in situ control of the temperature and chemical composition of the crystallization solution through dialysis, to generate crystals of the specific sizes required for different downstream structure determination approaches.

A new approach to variable-temperature measurements is presented, where the sample temperature changes continuously as a function of position.

The crystal structure of the mineral malayaite has been studied by single-crystal X-ray diffraction at a temperature of 20 K and by calculation of its phonon dispersion using density functional perturbation theory. The X-ray diffraction data show first-order satellite diffraction maxima at positions q = 0.2606 (8)b*, that are absent at room temperature. The computed phonon dispersion indicates unstable modes associated with dynamic displacements of the Ca atoms. The largest-frequency modulus of these phonon instabilities is located close to a wavevector of q = 0.3b*. These results indicate that the malayaite crystal structure is incommensurately modulated by static displacement of the Ca atoms at low temperatures, caused by the softening of an optic phonon with Bg symmetry.

The crystal structure of malayaite, CaSnOSiO4, at T = 20 K has been refined, based on the presence of satellite reflections with a modulation vector of 0.26b*. The structural modulation is attributed to a soft optic phonon, dominated by motion of the Ca atoms.

The study found that infants whose mothers had higher levels of available milk energy soon after their birth, coped more effectively (moved around more, explored more, ate and drank) and showed greater confidence (were more playful, exploratory, curious and active) with this novel situation.

The post New study sees mother’s milk as a communications link that shapes infant temperament appeared first on Smithsonian Insider.

A recent experiment by scientists at the Smithsonian Tropical Research Institute in Panama has revealed just how rising atmospheric carbon dioxide will deliver a one-two […]

The post Rising ocean temperatures and acidity may deliver deadly one-two punch to the world’s corals appeared first on Smithsonian Insider.

There is a new candidate for coldest known star: a brown dwarf with about the same temperature as a hot cup of coffee. That’s cool enough to begin crossing the blurry line between small cold stars and big hot planets.

The post New candidate for “coldest star” is same temperature as a hot cup of coffee appeared first on Smithsonian Insider.

The Harvard-Smithsonian Center for Astrophysics has been selected by the National Science Foundation as the recipient of a 12-meter (39-foot) radio antenna designed for submillimeter-wavelength astronomy. The ALMA Vertex Prototype Antenna was one of three antennas built as prototypes for the Atacama Large Millimeter Array, a 66-dish radio observatory currently being constructed in Chile.

The post Harvard-Smithsonian Center for Astrophysics to own and operate ALMA Vertex Prototype Antenna appeared first on Smithsonian Insider.

Hellbenders, aquatic salamanders from the eastern United States, are surprisingly good at dealing with unpredictable weather. In a recent study published in the Journal of […]

The post Zoo scientists find sudden stream temperature changes boost hellbender immune systems appeared first on Smithsonian Insider.

Warming temperatures may mean more generations of monarch butterflies in North America during summer months, say scientists who recently finished experiments with monarch caterpillars and […]

The post Warming temperatures may mean more monarch generations in some areas of North America appeared first on Smithsonian Insider.

Christian Renz, Veronique Albanese, Vera Tröster, Thomas K. Albert, Olivier Santt, Susan C. Jacobs, Anton Khmelinskii, Sebastien Leon, and Helle D. Ulrich

Polyubiquitin chains linked via lysine (K) 63 play an important role in endocytosis and membrane trafficking. Their primary source is the ubiquitin protein ligase (E3) Rsp5/NEDD4, which acts as a key regulator of membrane protein sorting. The heterodimeric ubiquitin-conjugating enzyme (E2), Ubc13-Mms2, catalyses K63-specific polyubiquitylation in genome maintenance and inflammatory signalling. In budding yeast, the only ubiquitin protein ligase (E3) known to cooperate with Ubc13-Mms2 so far is a nuclear RING finger protein, Rad5, involved in the replication of damaged DNA. We now report a contribution of Ubc13-Mms2 to the sorting of membrane proteins to the yeast vacuole via the multivesicular body (MVB) pathway. In this context, Ubc13-Mms2 cooperates with Pib1, a FYVE-RING finger protein associated with internal membranes. Moreover, we identified a family of membrane-associated FYVE-(type)-RING finger proteins as cognate E3s for Ubc13-Mms2 in several species, and genetic analysis indicates that the contribution of Ubc13-Mms2 to membrane trafficking in budding yeast goes beyond its cooperation with Pib1. Thus, our results widely implicate Ubc13-Mms2 as an Rsp5-independent source of K63-linked polyubiquitin chains in the regulation of membrane protein sorting.

Timelapse video of Flight operations aboard the USS Dwight D. Eisenhower brought to you by the Smithsonian’s National Air and Space Museum.

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The North Pole isn’t the only place on Earth affected by slight increases in temperature. Until recently, scientific thinking used to posit that tropical forests, […]

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As mangrove trees lose ground to deforestation and urban sprawl, one development seems to be giving them a boost: climate change. Fewer winter cold snaps […]

The post Mangroves creep north in response to warmer temperatures appeared first on Smithsonian Insider.

When the Signal Editor is saving data, the indicator that the save is occurring does not appear.  You might notice a delay when saving large data files.This bug exists in the following release(s):
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The title com­pound, tetra­ethyl­ammonium tetra­thio­rhenate, [(C2H5)4N][ReS4], has, at room temperature, a disordered structure in the space group P63mc (Z = 2, α-phase). A phase transition to the monoclinic space group P21 (Z = 2, γ-phase) at 285 K leads to a pseudo-merohedral twin. The high deviation from the hexa­gonal metric causes split reflections. However, the different orientations could not be separated, but were integrated using a large integration box. Rapid cooling to 110–170 K produces a metastable β-phase (P63, Z = 18) in addition to the γ-phase. All crystals of the β-phase are contaminated with the γ-phase. Additionally, the crystals of the β-phase are merohedrally twinned. In contrast to the α-phase, the β- and γ-phases do not show disorder.

To enhance the vitality and overall operation of the nations patent system, federal officials should take decisive steps to increase the systems flexibility, openness, and reliability, says a new report from the National Academies National Research Council.

There is sufficient evidence from tree rings, boreholes, retreating glaciers, and other proxies of past surface temperatures to say with a high level of confidence that the last few decades of the 20th century were warmer than any comparable period in the last 400 years, according to a new report from the National Research Council.

While every mode of transportation in the U.S. will be affected as the climate changes, potentially the greatest impact on transportation systems will be flooding of roads, railways, transit systems, and airport runways in coastal areas because of rising sea levels and surges brought on by more intense storms, says a new report from the National Research Council.

Over the last 25 years, deep-water oil and gas production in the Gulf of Mexico has increased significantly.

To transform the offshore oil and gas industry’s safety culture, operators, contractors, subcontractors, associations representing these groups, and federal regulators should collaborate to foster safety throughout all levels of the industry and confront challenges collectively, says a new report from the National Academies of Sciences, Engineering, and Medicine.

Consumer access to effective and affordable medicines is an imperative for public health, social equity, and economic development, but this need is not being served adequately by the biopharmaceutical sector, says a new report from the National Academies of Sciences, Engineering, and Medicine.

The U.S. Department of the Interior’s Bureau of Safety and Environmental Enforcement has ordered the National Academies of Sciences, Engineering, and Medicine to suspend all work on a study to review and update the bureau’s offshore oil and gas operations inspection program to enhance safety.

The Transportation Research Board’s Airport Cooperative Research Program (ACRP) recently selected winners for its University Design Competition for Addressing Airport Needs.

While health care has made great strides in recent years with the proliferation of electronic health records (EHRs), establishment of regional health information exchanges, and development of data exchange standards and interfaces, interoperability among health care technologies remains very limited, says a new National Academy of Medicine (NAM) special publication.

The president of the Russian Academy of Sciences (RAS) and the presidents of the U.S. National Academy of Sciences (NAS), U.S. National Academy of Engineering (NAE), and U.S. National Academy of Medicine (NAM) have signed a five-year agreement to continue their cooperation on studies, workshops, and other activities in areas of mutual interest.

The supercritical water oxidation (SCWO) system is a secondary waste processing reactor of the Blue Grass Chemical Agent Destruction Pilot Plant (BGCAPP). It is perhaps second in importance behind the agent neutralization reactors, which perform base hydrolysis of chemical warfare agents stored at the Blue Grass Army Depot.

The nation’s highways and roads connect almost 330 million Americans and are important to both commerce and national security. Two-thirds of total passenger travel in the country moves along this vast network of roads, as does 60 percent of the weight and almost three-quarters of the value of total U.S. freight transported.

A new rapid expert consultation from a standing committee of the National Academies of Sciences, Engineering, and Medicine responds to questions from the White House Office of Science and Technology Policy (OSTP) regarding survival of the COVID-19 virus in relation to temperature and humidity and potential for seasonal reduction and resurgence of cases.

As a novel coronavirus spreads throughout the world and the number of cases and deaths continues to rise, almost no country or community remains untouched by this rapidly evolving threat.