Fast radio bursts (FRBs) are brief spurts of radio emission, lasting just one-thousandth of a second, whose origins are mysterious. Fewer than two dozen have […]

The post Astronomers propose cell phone search for galactic radio bursts appeared first on Smithsonian Insider.

To fully know a species and develop sound conservation efforts, its full life cycle must be understood. But tracking small migratory birds for thousands of […]

The post Keeping Track of Kirtland’s Warbler All Year Long―A Scientific First appeared first on Smithsonian Insider.

For centuries, cultures around the world have used masks in ritual dances and festivals to represent traditional characters. This copper mask, found in the Smithsonian’s […]

The post Mexican Masks: Tales Through Dance appeared first on Smithsonian Insider.

The search for extraterrestrial intelligence has looked for many different signs of alien life, from radio broadcasts to laser flashes, without success. However, newly published […]

The post Could Fast Radio Bursts Be Powering Alien Probes? appeared first on Smithsonian Insider.

New species don’t just spring out of thin air. Speciation, the evolutionary process by which new and distinct species arise, usually takes millions of years. […]

The post Simultaneous hermaphrodites: Understanding Speciation in fish called “hamlets” appeared first on Smithsonian Insider.

A bizarre change occurs in the mouth of a humpback whale during its development in the womb. Several dozen tooth buds sprout in a row […]

The post Paleo-detectives energize great whale mystery: how & when baleen evolved appeared first on Smithsonian Insider.

Whales from both poles migrate long distances to breed in tropical waters. Smithsonian scientist Hector M. Guzman and Fernando Félix at the Salinas Whale Museum […]

The post Whale tagging in Southeast Pacific provides data for species protection appeared first on Smithsonian Insider.

Fetching close to $1,500 per pound, ivory ranks fourth in black-market traded items just behind illegal drugs, weapons, and humans. Governments across the globe are […]

The post New technique may help authorities quickly ID real and fake ivory products appeared first on Smithsonian Insider.

The blue whale, which uses baleen to filter its prey from ocean water and can reach lengths of over 100 feet, is the largest vertebrate […]

The post Only recently did whales become giant appeared first on Smithsonian Insider.

AUSTIN, Texas — Astronomers at The University of Texas at Austin and Harvard University have put a basic principle of black holes to the test, […]

The post Do Stars Fall Quietly into Black Holes? appeared first on Smithsonian Insider.

Finding clean ways to store water is a challenge that humans have faced for millennia. In a new paper in Environmental Health, anthropologist Sabrina Sholts […]

The post Study shows ancient California Indians risked toxins from bitumen-coated bottles appeared first on Smithsonian Insider.

Two separate teams of scientists have identified major challenges for the development of life in what has recently become one of the most famous exoplanet […]

The post There’s more to extraterrestrial life than planets in “habitable zone” orbits appeared first on Smithsonian Insider.

Great Cats keepers at the Smithsonian’s National Zoo are celebrating the birth of a Sumatran tiger, a critically endangered species. The cub’s mother, 8-year-old Damai, […]

The post Sumatran tiger cub born National Zoo appeared first on Smithsonian Insider.

Using new numerical simulations and observations, scientists may now be able to explain why the Sun’s magnetic field reverses every eleven years. This significant discovery […]

The post 3D simulations reveals why the Sun flips its magnetic field every 11 years appeared first on Smithsonian Insider.

The next time you swat a fly ponder this: inside its belly is the DNA of whatever it ate before landing on your picnic dinner—roadkill, […]

The post Innovation: Belly gunk from flies used to survey forest animals appeared first on Smithsonian Insider.

Covered in sharp spines, when harassed the porcupine fish inflates like a balloon. Think of a small soccer ball bristling all over with nails. Most predators […]

The post Indestructible jaws from ancient, extinct porcupine fish reveal new species appeared first on Smithsonian Insider.

Cats are notoriously fickle—purring in your lap one second, then swiping you with an indignant claw the next. One thing is certain however when it […]

The post Eons before viral kitten videos, ancient Egyptians adored cats appeared first on Smithsonian Insider.

Plastic debris floating in the ocean has become a powerful new passport to far-away destinations for a wide variety of invasive species, according to new […]

The post Tsunami reveals drifting ocean plastic opens globe to invasive castaways appeared first on Smithsonian Insider.

Chances are, if you’ve been stung by a jellyfish along the Chesapeake Bay it was by a sea nettle jellyfish–one of the most common and […]

The post Scientists discover common sea nettle jellyfish is actually two distinct species appeared first on Smithsonian Insider.

This animation shows how binary neutron stars warp space-time to create gravitational waves, then collide and explode into a visible kilonova, which can be detected […]

The post Astronomers see light show associated with gravitational waves appeared first on Smithsonian Insider.

The next generation of the Sloan Digital Sky Survey (SDSS-V), directed by Juna Kollmeier of the Carnegie Institution for Science, will move forward with mapping […]

The post Next generation astronomical survey to map the entire sky appeared first on Smithsonian Insider.

A new project using data from NASA’s Chandra X-ray Observatory and other telescopes allows people to navigate through real data of the remains of an […]

The post A new stellar X-ray “reality” show debuts appeared first on Smithsonian Insider.

The center of our Galaxy has been intensely studied for many years, but it still harbors surprises for scientists. A snake-like structure lurking near our […]

The post Cosmic filament probes our galaxy’s giant black hole appeared first on Smithsonian Insider.

One of Earth’s most evolutionarily unique species is also the world’s most trafficked mammal: pangolins, or “scaly anteaters.” A new study from the Smithsonian Conservation […]

The post Using genetics to help save world’s most trafficked mammal: the pangolin appeared first on Smithsonian Insider.

In the past 50 years, the amount of water in the open ocean with zero oxygen has increased more than fourfold. In coastal water bodies, […]

The post Earth’s oceans are losing their breath. Here’s the global scope appeared first on Smithsonian Insider.

Swimming in the frigid waters of the Arctic and surfacing in narrow gaps in the sea ice to breathe, the narwhal is one of the […]

The post Meet the world’s weirdest whale appeared first on Smithsonian Insider.

Animal species can become endangered, but what about languages? Around 80 percent of the world’s population speaks just 20 percent of its 7,000 languages. That […]

The post Why languages become endangered, and how we can keep them alive appeared first on Smithsonian Insider.

When “2001: A Space Odyssey” premiered April 2, 1968 at Washington, D.C.’s Uptown Theater—not far from the Smithsonian’s National Air and Space Museum—not everyone was […]

The post The real history behind science fiction’s ‘2001: A Space Odyssey’ appeared first on Smithsonian Insider.

People often use the words turtle and tortoise interchangeably, but these reptiles have distinct differences: Turtle shells are typically more flattened and not as deeply […]

The post Five fun turtle and tortoise facts from the Smithsonian’s National Zoo appeared first on Smithsonian Insider.

 Extinct species don’t usually get a do-over… but don’t tell that to the scimitar-horned oryx. Erased from the wild for three decades, these desert […]

The post Podcast: Don’t call me extinct appeared first on Smithsonian Insider.

Every queen deserves a castle, and the ruler of the Smithsonian’s National Zoo’s naked mole-rat colony is no different. After 27 years in a maze […]

The post Building a naked mole-rat dream home at the Smithsonian’s National Zoo appeared first on Smithsonian Insider.

When the heat and humidity of the Washington, D.C. summer sends its residents scrambling for air conditioning and iced coffee, the animal care specialists at […]

The post How do National Zoo animals beat the heat? Bloodsicles and other frozen delicacies appeared first on Smithsonian Insider.

l-Hydroxyproline (l-Hyp) is a nonstandard amino acid that is present in certain proteins, in some antibiotics and in the cell-wall components of plants. l-Hyp is the product of the post-translational modification of protein prolines by prolyl hydroxylase enzymes, and the isomers trans-3-hydroxy-l-proline (T3LHyp) and trans-4-hydroxy-l-proline (T4LHyp) are major components of mammalian collagen. T4LHyp follows two distinct degradation pathways in bacteria and mammals, while T3LHyp is metabolized by a two-step metabolic pathway that is conserved in bacteria and mammals, which involves a T3LHyp dehydratase and a Δ1-pyrroline-2-carboxylate (Pyr2C) reductase. In order to shed light on the structure and catalysis of the enzyme involved in the second step of the T3LHyp degradation pathway, the crystal structure of Pyr2C reductase from the archaeon Thermococcus litoralis DSM 5473 complexed with NADH and l-proline is presented. The model allows the mapping of the residues involved in cofactor and product binding and represents a valid model for rationalizing the catalysis of Pyr2C reductases.

The outer membrane of Gram-negative bacteria is highly impermeable to hydrophilic molecules of larger than 600 Da, protecting these bacteria from toxins present in the environment. In order to transport nutrients across this impermeable membrane, Gram-negative bacteria utilize a diverse family of outer-membrane proteins called TonB-dependent transporters. The majority of the members of this family transport iron-containing substrates. However, it is becoming increasingly clear that TonB-dependent transporters target chemically diverse substrates. In this work, the structure and phylogenetic distribution of the TonB-dependent transporter YncD are investigated. It is shown that while YncD is present in some enteropathogens, including Escherichia coli and Salmonella spp., it is also widespread in Gammaproteobacteria and Betaproteobacteria of environmental origin. The structure of YncD was determined, showing that despite a distant evolutionary relationship, it shares structural features with the ferric citrate transporter FecA, including a compact positively charged substrate-binding site. Despite these shared features, it is shown that YncD does not contribute to the growth of E. coli in pure culture under iron-limiting conditions or with ferric citrate as an iron source. Previous studies of transcriptional regulation in E. coli show that YncD is not induced under iron-limiting conditions and is unresponsive to the ferric uptake regulator (Fur). These observations, combined with the data presented here, suggest that YncD is not responsible for the transport of an iron-containing substrate.

Aldo-keto reductases (AKRs) are NADPH/NADP+-dependent oxidoreductase enzymes that metabolize an aldehyde/ketone to the corresponding alcohol. AKR4C14 from rice exhibits a much higher efficiency in metabolizing malondialdehyde (MDA) than do the Arabidopsis enzymes AKR4C8 and AKR4C9, despite sharing greater than 60% amino-acid sequence identity. This study confirms the role of rice AKR4C14 in the detoxification of methylglyoxal and MDA, and demonstrates that the endogenous contents of both aldehydes in transgenic Arabidopsis ectopically expressing AKR4C14 are significantly lower than their levels in the wild type. The apo structure of indica rice AKR4C14 was also determined in the absence of the cofactor, revealing the stabilized open conformation. This is the first crystal structure in AKR subfamily 4C from rice to be observed in the apo form (without bound NADP+). The refined AKR4C14 structure reveals a stabilized open conformation of loop B, suggesting the initial phase prior to cofactor binding. Based on the X-ray crystal structure, the substrate- and cofactor-binding pockets of AKR4C14 are formed by loops A, B, C and β1α1. Moreover, the residues Ser211 and Asn220 on loop B are proposed as the hinge residues that are responsible for conformational alteration while the cofactor binds. The open conformation of loop B is proposed to involve Phe216 pointing out from the cofactor-binding site and the opening of the safety belt. Structural comparison with other AKRs in subfamily 4C emphasizes the role of the substrate-channel wall, consisting of Trp24, Trp115, Tyr206, Phe216, Leu291 and Phe295, in substrate discrimination. In particular, Leu291 could contribute greatly to substrate selectivity, explaining the preference of AKR4C14 for its straight-chain aldehyde substrate.

The biological processes related to protein homeostasis in Mycobacterium tuberculosis, the etiologic agent of tuberculosis, have recently been established as critical pathways for therapeutic intervention. Proteins of particular interest are ClpC1 and the ClpC1–ClpP1–ClpP2 proteasome complex. The structure of the potent antituberculosis macrocyclic depsipeptide ecumicin complexed with the N-terminal domain of ClpC1 (ClpC1-NTD) is presented here. Crystals of the ClpC1-NTD–ecumicin complex were monoclinic (unit-cell parameters a = 80.0, b = 130.0, c = 112.0 Å, β = 90.07°; space group P21; 12 complexes per asymmetric unit) and diffracted to 2.5 Å resolution. The structure was solved by molecular replacement using the self-rotation function to resolve space-group ambiguities. The new structure of the ecumicin complex showed a unique 1:2 (target:ligand) stoichiometry exploiting the intramolecular dyad in the α-helical fold of the target N-terminal domain. The structure of the ecumicin complex unveiled extensive interactions in the uniquely extended N-terminus, a critical binding site for the known cyclopeptide complexes. This structure, in comparison with the previously reported rufomycin I complex, revealed unique features that could be relevant for understanding the mechanism of action of these potential antituberculosis drug leads. Comparison of the ecumicin complex and the ClpC1-NTD-L92S/L96P double-mutant structure with the available structures of rufomycin I and cyclomarin A complexes revealed a range of conformational changes available to this small N-terminal helical domain and the minor helical alterations involved in the antibiotic-resistance mechanism. The different modes of binding and structural alterations could be related to distinct modes of action.

Pullulanase (EC 3.2.1.41) is a well known starch-debranching enzyme that catalyzes the cleavage of α-1,6-glycosidic linkages in α-glucans such as starch and pullulan. Crystal structures of a type I pullulanase from Paenibacillus barengoltzii (PbPulA) and of PbPulA in complex with maltopentaose (G5), maltohexaose (G6)/α-cyclodextrin (α-CD) and β-cyclodextrin (β-CD) were determined in order to better understand substrate binding to this enzyme. PbPulA belongs to glycoside hydrolase (GH) family 13 subfamily 14 and is composed of three domains (CBM48, A and C). Three carbohydrate-binding sites identified in PbPulA were located in CBM48, near the active site and in domain C, respectively. The binding site in CBM48 was specific for β-CD, while that in domain C has not been reported for other pullulanases. The domain C binding site had higher affinity for α-CD than for G6; a small motif (FGGEH) seemed to be one of the major determinants for carbohydrate binding in this domain. Structure-based mutations of several surface-exposed aromatic residues in CBM48 and domain C had a debilitating effect on the activity of the enzyme. These results suggest that both CBM48 and domain C play a role in binding substrates. The crystal forms described contribute to the understanding of pullulanase domain–carbohydrate interactions.

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 bond-valence method has been used for valence calculations of FeMo/V cofactors in FeMo/V proteins using 51 crystallographic data sets of FeMo/V proteins from the Protein Data Bank. The calculations show molybdenum(III) to be present in MoFe7S9C(Cys)(HHis)[R-(H)homocit] (where H4homocit is homocitric acid, HCys is cysteine and HHis is histidine) in FeMo cofactors, while vanadium(III) with a more reduced iron complement is obtained for FeV cofactors. Using an error analysis of the calculated valences, it was found that in FeMo cofactors Fe1, Fe6 and Fe7 can be unambiguously assigned as iron(III), while Fe2, Fe3, Fe4 and Fe5 show different degrees of mixed valences for the individual Fe atoms. For the FeV cofactors in PDB entry 5n6y, Fe4, Fe5 and Fe6 correspond to iron(II), iron(II) and iron(III), respectively, while Fe1, Fe2, Fe3 and Fe7 exhibit strongly mixed valences. Special situations such as CO-bound and selenium-substituted FeMo cofactors and O(N)H-bridged FeV cofactors are also discussed and suggest rearrangement of the electron configuration on the substitution of the bridging S atoms.

Mycoplasma hyopneumoniae is a prokaryotic pathogen that colonizes the respiratory ciliated epithelial cells in swine. Infected animals suffer respiratory lesions, causing major economic losses in the porcine industry. Characterization of the immunodominant membrane-associated proteins from M. hyopneumoniae may be instrumental in the development of new therapeutic approaches. Here, the crystal structure of P46, one of the main surface-antigen proteins, from M. hyopneumoniae is presented and shows N- and C-terminal α/β domains connected by a hinge. The structures solved in this work include a ligand-free open form of P46 (3.1 Å resolution) and two ligand-bound structures of P46 with maltose (2.5 Å resolution) and xylose (3.5 Å resolution) in open and closed conformations, respectively. The ligand-binding site is buried in the cleft between the domains at the hinge region. The two domains of P46 can rotate with respect to each other, giving open or closed alternative conformations. In agreement with this structural information, sequence analyses show similarities to substrate-binding members of the ABC transporter superfamily, with P46 facing the extracellular side as a functional subunit. In the structure with xylose, P46 was also bound to a high-affinity (Kd = 29 nM) Fab fragment from a monoclonal antibody, allowing the characterization of a structural epitope in P46 that exclusively involves residues from the C-terminal domain. The Fab structure in the complex with P46 shows only small conformational rearrangements in the six complementarity-determining regions (CDRs) with respect to the unbound Fab (the structure of which is also determined in this work at 1.95 Å resolution). The structural information that is now available should contribute to a better understanding of sugar nutrient intake by M. hyopneumoniae. This information will also allow the design of protocols and strategies for the generation of new vaccines against this important swine pathogen.

Leucocyte common antigen-related protein (LAR) is a post-synaptic type I transmembrane receptor protein that is important for neuronal functionality and is genetically coupled to neuronal disorders such as attention deficit hyperactivity disorder (ADHD). To understand the molecular function of LAR, structural and biochemical studies of protein fragments derived from the ectodomain of human LAR have been performed. The crystal structure of a fragment encompassing the first four FNIII domains (LARFN1–4) showed a characteristic L shape. SAXS data suggested limited flexibility within LARFN1–4, while rigid-body refinement of the SAXS data using the X-ray-derived atomic model showed a smaller angle between the domains defining the L shape compared with the crystal structure. The capabilities of the individual LAR fragments to interact with heparin was examined using microscale thermophoresis and heparin-affinity chromatography. The results showed that the three N-terminal immunoglobulin domains (LARIg1–3) and the four C-terminal FNIII domains (LARFN5–8) both bound heparin, while LARFN1–4 did not. The low-molecular-weight heparin drug Innohep induced a shift in hydrodynamic volume as assessed by size-exclusion chromatography of LARIg1–3 and LARFN5–8, while the chemically defined pentameric heparin drug Arixtra did not. Together, the presented results suggest the presence of an additional heparin-binding site in human LAR.