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.

Transforming growth factor β-1 (TGFβ-1) is a secreted signalling protein that directs many cellular processes and is an attractive target for the treatment of several diseases. The primary endogenous activity regulatory mechanism for TGFβ-1 is sequestration by its pro-peptide, latency-associated peptide (LAP), which sterically prohibits receptor binding by caging TGFβ-1. As such, recombinant LAP is promising as a protein-based therapeutic for modulating TGFβ-1 activity; however, the mechanism of binding is incompletely understood. Comparison of the crystal structure of unbound LAP (solved here to 3.5 Å resolution) with that of the bound complex shows that LAP is in a more open and extended conformation when unbound to TGFβ-1. Analysis suggests a mechanism of binding TGFβ-1 through a large-scale conformational change that includes contraction of the inter-monomer interface and caging by the `straight-jacket' domain that may occur in partnership through a loop-to-helix transition in the core jelly-roll fold. This conformational change does not appear to include a repositioning of the integrin-binding motif as previously proposed. X-ray scattering-based modelling supports this mechanism and reveals possible orientations and ensembles in solution. Although native LAP is heavily glycosylated, solution scattering experiments show that the overall folding and flexibility of unbound LAP are not influenced by glycan modification. The combination of crystallography, solution scattering and biochemical experiments reported here provide insight into the mechanism of LAP sequestration of TGFβ-1 that is of fundamental importance for therapeutic development.

The open-source Python program PDB2INS is designed to prepare a .ins file for refinement with SHELXL [Sheldrick (2015). Acta Cryst. C71, 3–8], taking atom coordinates and other information from a Protein Data Bank (PDB)-format file. If PDB2INS is provided with a four-character PDB code, both the PDB file and the accompanying mmCIF-format reflection data file (if available) are accessed via the internet from the PDB public archive [Read et al. (2011). Structure, 19, 1395–1412] or optionally from the PDB_REDO server [Joosten, Long, Murshudov & Perrakis (2014). IUCrJ, 1, 213–220]. The SHELX-format .ins (refinement instructions and atomic coordinates) and .hkl (reflection data) files can then be generated without further user intervention, appropriate restraints etc. being added automatically. PDB2INS was tested on the 23 974 X-ray structures deposited in the PDB between 2008 and 2018 that included reflection data to 1.7 Å or better resolution in a recognizable format. After creating the two input files for SHELXL without user intervention, ten cycles of conjugate-gradient least-squares refinement were performed. For 96% of these structures PDB2INS and SHELXL completed successfully without error messages.

Because researchers do not understand the formation mechanism of cocrystals, the preparation of cocrystals is mostly done by trial and error. This study focuses on the cocrystal formation mechanism to improve the efficiency of cocrystal preparation.

The sin2ψ and cosα methods are compared via diffracting-grain identification from electron backscatter diffraction maps. Artificial textures created by the X-ray diffraction measurements are plotted and X-ray elastic constants of the diffracting-grain sets are computed.

In recent research on Santa Rosa Island off the coast of Southern California, isotope readings of carbon and nitrogen found in the bones of Chumash Indians and domestic dogs excavated from archaeological sites show that both humans and dogs have nearly identical signatures of stable isotopes.

The post Ancient bond between humans and dogs revealed in isotopic signatures of their bones appeared first on Smithsonian Insider.

Imagine a gas giant planet spanning three times more sky than the Moon looming over the molten landscape of a lava world. This alien vista exists in the newly discovered two-planet system of Kepler-36.

The post Close encounters between planetary systems of Kepler-36 stun astrophysicists appeared first on Smithsonian Insider.

Astronomers are constantly on the hunt for ever-colder star-like bodies, and two years ago a new class of objects was discovered by researchers using NASA’s […]

The post Coldest brown dwarfs blur lines between stars and planets appeared first on Smithsonian Insider.

The majestic feathers of the greater bird of paradise (Paradisaea apoda) have inspired people for thousands of years. Like many birds on the isolated island […]

The post Feathers of seduction – the connection between birds and people of New Guinea appeared first on Smithsonian Insider.

New research by a team of archaeologists has revealed a curious connection between our traditional Thanksgiving dinner and the taste buds of prehistoric mammoths and […]

The post Study reveals ancient link between mammoth dung and pumpkin pie appeared first on Smithsonian Insider.

Food is scarce in the deep, dark regions of the ocean where barbeled dragonfishes and their relatives dwell. Known as the Stomiidae, some of these […]

The post Odd anatomy: flexible joint between skull and spine allow dragonfish to open wide appeared first on Smithsonian Insider.

Death-associated protein kinase 1 (DAPK1) is a serine/threonine protein kinase that regulates apoptosis and autophagy. DAPK1 is considered to be a therapeutic target for amyloid-β deposition, endometrial adenocarcinomas and acute ischemic stroke. Here, the potent inhibitory activity of the natural anthraquinone purpurin against DAPK1 phosphorylation is shown. Thermodynamic analysis revealed that while the binding affinity of purpurin is similar to that of CPR005231, which is a DAPK1 inhibitor with an imidazopyridazine moiety, the binding of purpurin was more enthalpically favorable. In addition, the inhibition potencies were correlated with the enthalpic changes but not with the binding affinities. Crystallographic analysis of the DAPK1–purpurin complex revealed that the formation of a hydrogen-bond network is likely to contribute to the favorable enthalpic changes and that stabilization of the glycine-rich loop may cause less favorable entropic changes. The present findings indicate that purpurin may be a good lead compound for the discovery of inhibitors of DAPK1, and the observation of enthalpic changes could provide important clues for drug development.

The humble salamander may provide evidence to support a controversial claim that North and South America were joined together much earlier than previously thought. The […]

The post Salamander DNA reveals evidence of older land connection between Central and South America appeared first on Smithsonian Insider.

Scientists from the Smithsonian and the University of Rhode Island have found unsuspected linkages between the oxidation state of iron in volcanic rocks and variations […]

The post Scientists uncover relationship between lavas erupting on sea floor and deep-carbon cycle appeared first on Smithsonian Insider.

Long ago, one great ocean flowed between North and South America. When the narrow Isthmus of Panama joined the continents about 3 million years ago, […]

The post Recent Connection Between North and South America Reaffirmed appeared first on Smithsonian Insider.

A limited body of evidence suggests an association between military service and later development of amyotrophic lateral sclerosis (ALS), a rare but fatal neurodegenerative disorder, says a new report from the Institute of Medicine.

A new report from the Institute of Medicine finds suggestive but limited evidence that exposure to Agent Orange and other herbicides used during the Vietnam War is associated with an increased chance of developing high blood pressure in some veterans.

Short-term exposure to current levels of ozone in many areas is likely to contribute to premature deaths, says a new National Research Council report, which adds that the evidence is strong enough that the U.S. Environmental Protection Agency should include ozone-related mortality in health-benefit analyses related to future ozone standards.

A new report from the Institute of Medicine finds suggestive but limited evidence that exposure to Agent Orange and other herbicides used during the Vietnam War is associated with an increased chance of developing ischemic heart disease and Parkinsons disease for Vietnam veterans.

Insufficient sleep can decrease a commercial motor vehicle (CMV) driver’s level of alertness, which may increase the risk of a crash, yet little is known about effective ways to minimize that risk, says a new report from the National Academies of Sciences, Engineering, and Medicine.

The number of patients in the U.S. awaiting organ transplantation outpaces the amount of transplants performed in the U.S., and many donated organs are not transplanted each year due to several factors, such as poor organ function, says a new report from the National Academies of Sciences, Engineering, and Medicine.

Renewed interest in exploration of the moon has the potential to benefit lunar science greatly and could evolve into a program facilitated by partnerships between commercial companies and NASA’s Science Mission Directorate (SMD), say companion reports by the National Academies of Sciences, Engineering, and Medicine.

Although the immediate side effects of antimalarial drugs are widely recognized, few studies were designed specifically to examine health problems that might occur or persist months or years after people stopped taking them.

Argentina-based fintech Mercado Pago has announced it will now be possible to share...

Assessing the potential of new environmental management tools often brings an ???innovation dilemma???: is it better to stick with what is known to work, or to implement new measures that are potentially more effective, but also more uncertain? Researchers have proposed an approach to deal with these dilemmas, and applied it to the case study of an invasive species programme in the US.

Marine Protected Areas should be managed as integrated networks rather than isolated units because of the high degree of exchange between them, a new study suggests. The researchers found that the large majority of sea bream (Sparidae) and wrasse (Labridae) fish spawned in MPA study sites in the Mediterranean Sea were transported via currents to other MPAs and unprotected areas, highlighting their interconnected nature.

Long ago, one great ocean flowed between North and South America. When the narrow Isthmus of Panama joined the continents about 3 million years ago, it also separated the Atlantic from the Pacific Ocean. If this took place millions of years earlier, as recently asserted by some, the implications for both land and sea life would be revolutionary. Aaron O'Dea, staff scientist at the Smithsonian Tropical Research Institute (STRI), and colleagues writing in Science Advances firmly set the date at 2.8 million years ago.

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An international team of scientists has described a rare fossil site that is believed to be among the earliest evidence of different fish species using a common nursery -- much like ones utilized by some fish today.

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Little difference was found between organically grown tomatoes and tomatoes grown conventionally in greenhouses over a three year period, in terms of taste and nutritional value, according to a recent study in the Netherlands. Taste and nutrition were more dependent on the breed of tomato.

UN researchers highlight the need to develop better ways to measure the impacts of climate change on children's health. They suggest more attention be given to impact analysis of different social groups and ages, as well as nutrition.

Energy efficiency is at the centre of EU policy for achieving a fundamental transformation of Europe’s energy systems by 2030. This Thematic Issue reveals the complexity of the issue of energy efficiency, its links with resource efficiency and the wide range of factors influencing it, from technology to social practices.

Shifts in species’ ranges are expected under climate change, as organisms move to find suitable conditions. New research in the Mediterranean Sea has found that the way species interact could also have a significant effect on their resilience in a changing climate.

Micro, small and medium-sized enterprises comprise the majority of European businesses — and, therefore, have a vital role to play in reducing our dependence on, and consumption of, increasingly scarce resources. A new study explores whether the concept of industrial symbiosis, in which companies use waste products of other industries as raw materials, is common in small- and medium-sized companies (SMEs) — using beer producers and mushroom farmers in Sweden as case studies.

Preliminary findings from a mass participation study have indicated a link between weather conditions - specifically rain and lack of sunshine - and chronic pain.

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A new UK study suggests that there are associations between obesity, physical activity, and levels of CO2 emissions from transport. These associations seem mostly to reflect the fact that obese people tend to travel longer distances by motorised forms of travel. They may also partly reflect less ‘active travel’ by bicycle or walking by obese people.

Hybrid and electric vehicles emit lower levels of carbon dioxide and air pollutants than conventional petrol and diesel vehicles, yet their market uptake in the EU remains limited. New research provides an assessment of the Total Cost of Ownership (TCO) — which combines purchase and operating expenses — of different vehicle types. By comparing historical data on hybrid, petrol and diesel vehicles in three countries (Japan, the UK and the USA), researchers found a strong link between TCO and market share of those vehicles. They also identified a number of ways in which policymakers may promote the adoption of cleaner vehicles through the provision of financial incentives.

It is crucial for CIOs to break free from set behaviors and relationships in order to establish IT as a full business partner. If CIOs complain that they feel ignored by the business, they are themselves to blame.

High levels of waste production must be tackled as part of the move towards sustainable living. Recent research has used Sweden as a case study to assess the strength of suitable policies and strategies that are required to break the link between economic growth and waste generation.

New research on sustainable forest management (SFM) initiatives in Russia and Sweden has indicated that the main challenges to SFM are combining top-down and bottom up approaches to management, coordinating the different sectors involved and including all actors and stakeholders.

New research has investigated the possibility of transferring policy between EU Member States. It studied the outcomes of an EU-funded project that aimed to integrate land use planning and transport management across Europe, and identified barriers to transfer, which included language, differing planning traditions and difficulties in systematically adopting a policy across a nation. The study also highlights a role for EU projects in beginning the process of policy transfer.

Renewable energy plays an important role in economic development, according to a recent study which investigated the relationship between economic growth and energy consumption in Europe.

Assessing the potential of new environmental management tools often brings an ‘innovation dilemma’: is it better to stick with what is known to work, or to implement new measures that are potentially more effective, but also more uncertain? Researchers have proposed an approach to deal with these dilemmas, and applied it to the case study of an invasive species programme in the US.

EU integration may have led to more sustainable consumption patterns in new Member States (NMS) during 1995-2007, according to researchers from Lithuania. Their study indicates that, during this period in new Member States, a smaller share of household expenditure was spent on ‘essential’, but more environmentally-damaging items, such as food, drink and housing, and a larger share on ‘luxurious’, but less environmentally damaging, items.

A lack of trust between stakeholders, planners and decision makers in coastal Portugal is obstructing adaptation to climate change plans, finds a new study. The researchers suggest that building trust between stakeholders and coastal managers could lead to improved participation and dialogue for future planning, financing and implementation of coastal adaptation.

The drive to increase renewable energy production can sometimes be at loggerheads with the desire to preserve natural landscapes. In this study, researchers from across Europe assessed the environmental impacts of renewable energies in the Alps, making key recommendations to resolve conflicts between different users of habitats.

Energy production uses large quantities of water and, in turn, water provision requires considerable amounts of energy. A new study has investigated the interconnection between water and energy, the ‘water-energy nexus’, in Spain and found that 5.8% of total electricity consumption is for water-use and 25% of water withdrawals are for energy generation.

A recent study suggests that a shift to more sustainable development, based on ecosystem services, is needed to support human health and wellbeing. Focusing on ecosystem services provided by river catchments, this study recommends that more needs to be done on a practical level to support decision-makers, in a way that recognises the relationships between different types of ecosystem services.

High Nature Value (HNV) farmland is agricultural land that supports biodiversity and can be identified by its environmentally sound farming practices. New research on bird biodiversity on French HNV farmland has concluded that conservation of HNV farmland is important as well as conserving areas that were previously HNV and have undergone recent agricultural intensification.