CrysFormer: Protein structure determination via Patterson maps, deep learning, and partial structure attention.

Determining the atomic-level structure of a protein has been a decades-long challenge. However, recent advances in transformers and related neural network architectures have enabled researchers to significantly improve solutions to this problem. These methods use large datasets of sequence information and corresponding known protein template structures, if available.

Heterotrimeric collagen helix with high specificity of assembly results in a rapid rate of folding.

The most abundant natural collagens form heterotrimeric triple helices. Synthetic mimics of collagen heterotrimers have been found to fold slowly, even compared to the already slow rates of homotrimeric helices. These prolonged folding rates are not understood.

Crystal structure of the photosensory module from a PAS-less cyanobacterial phytochrome as Pr shows a mix of dark-adapted and photoactivated features.

Phytochromes (Phys) are a diverse collection of photoreceptors that regulate numerous physiological and developmental processes in microorganisms and plants through photointerconversion between red-light-absorbing Pr and far-red light-absorbing Pfr states. Light is detected by an N-terminal photo-sensing module (PSM) sequentially comprised of Period/ARNT/Sim (PAS), cGMP-phosphodiesterase/adenylyl cyclase/FhlA (GAF), and Phy-specific (PHY) domains, with the bilin chromophore covalently-bound within the GAF domain. Phys sense light via the Pr/Pfr ratio measured by the light-induced rotation of the bilin D-pyrrole ring that triggers conformational changes within the PSM, which for microbial Phys reaches into an output region.

Lissajous curves as aerial search patterns.

Manned and unmanned systems are prevalent in a wide range of aerial searching applications. For aircraft whose trajectory is not or cannot be planned on-the-fly, optimal deterministic search pattern generation is a critical area of research. Lissajous curves have recently caught attention as excellent candidates for all kinds of aerial search applications, but little fundamental research has been done to understand how best to design Lissajous pattern (LP)s for this use.

Biochemical and Structural Studies of the Carminomycin 4--Methyltransferase DnrK.

Structural and functional studies of the carminomycin 4--methyltransferase DnrK are described, with an emphasis on interrogating the acceptor substrate scope of DnrK. Specifically, the evaluation of 100 structurally and functionally diverse natural products and natural product mimetics revealed an array of pharmacophores as productive DnrK substrates. Representative newly identified DnrK substrates from this study included anthracyclines, angucyclines, anthraquinone-fused enediynes, flavonoids, pyranonaphthoquinones, and polyketides.

Highly Solubilized Urea as Effective Proton Donor-Acceptors for Durable Zinc-Ion Storage Beyond Single-Anion Selection Criteria.

Urea, as one of the most sustainable organic solutes, denies the high salt consumption in commercial electrolytes with its peculiar solubility in water. The bi-mixture of urea-HO shows the eutectic feature for increased attention in aqueous Zn-ion electrochemical energy storage (AZEES) technologies. While the state-of-the-art aqueous electrolyte recipes are still pursuing the high-concentrated salt dosage with limited urea adoption and single-anion selection category.

A deep learning solution for crystallographic structure determination.

The general de novo solution of the crystallographic phase problem is difficult and only possible under certain conditions. This paper develops an initial pathway to a deep learning neural network approach for the phase problem in protein crystallography, based on a synthetic dataset of small fragments derived from a large well curated subset of solved structures in the Protein Data Bank (PDB). In particular, electron-density estimates of simple artificial systems are produced directly from corresponding Patterson maps using a convolutional neural network architecture as a proof of concept.

Does Utilizing IRIS, a Segmented Three-dimensional Model, Increase Surgical Precision During Robotic Partial Nephrectomy?

Purpose: Preservation of renal parenchyma is a major goal when performing a partial nephrectomy. IRIS anatomical visualization software generates a segmented 3D model, allowing improved visualization of the tumor and surrounding structures. We hypothesize that using IRIS intraoperatively during partial nephrectomy on complex tumors increases the precision of surgical procedures and therefore may result in more tissue preservation.

Targeted Hypoglossal Nerve Stimulation for Patients With Obstructive Sleep Apnea: A Randomized Clinical Trial.

Importance: Evidence is lacking from randomized clinical trials of hypoglossal nerve stimulation in obstructive sleep apnea (OSA).

Objective: To evaluate the safety and effectiveness of targeted hypoglossal nerve stimulation (THN) of the proximal hypoglossal nerve in patients with OSA.

Design, Setting, And Participants: This randomized clinical trial (THN3) was conducted at 20 centers and included 138 patients with moderate to severe OSA with an apnea-hypopnea index (AHI) of 20 to 65 events per hour and body mass index (calculated as weight in kilograms divided by height in meters squared) of 35 or less.

An NmrA-like enzyme-catalysed redox-mediated Diels-Alder cycloaddition with anti-selectivity.

The Diels-Alder cycloaddition is one of the most powerful approaches in organic synthesis and is often used in the synthesis of important pharmaceuticals. Yet, strictly controlling the stereoselectivity of the Diels-Alder reactions is challenging, and great efforts are needed to construct complex molecules with desired chirality via organocatalysis or transition-metal strategies. Nature has evolved different types of enzymes to exquisitely control cyclization stereochemistry; however, most of the reported Diels-Alderases have been shown to only facilitate the energetically favourable diastereoselective cycloadditions.

COVID, Crime & Criminal Justice: Affirming the Call for System Reform Research.

Early into the COVID-19 pandemic, Miller & Blumstein (2020) outlined a theoretical research program (TRP) oriented around themes of contagion control and containment, legal amnesty, system leniency, nonenforcement, and tele-justice. Here, two and a half years later, these lingering themes are revisited to advocate for empirical research informing criminal justice system reform. The pandemic created rare natural experiment research conditions that enable unique and potentially valuable insights on necessitated innovations that may indicate future justice practices and policies.

Treatment of obstructive sleep apnea with hypoglossal nerve stimulation in a patient with Ehlers-Danlos syndrome.

Unlabelled: Ehlers-Danlos syndrome is a group of hereditary connective tissue disorders caused by defects in collagen synthesis and structure that manifests as tissue fragility, hypermobility, and vascular abnormalities. Patients with Ehlers-Danlos syndrome are at a high risk of developing obstructive sleep apnea due to increased tissue laxity in the upper airway, in addition to nasal-maxillary cartilaginous defects, scoliosis, or other abnormalities. Here we present the case of a patient with Ehlers-Danlos syndrome who underwent successful treatment of obstructive sleep apnea using hypoglossal nerve stimulation after continuous positive airway pressure therapy failure, demonstrating that this can be a useful treatment modality in this population.

Expanding the eukaryotic genetic code with a biosynthesized 21st amino acid.

Genetic code expansion technology allows for the use of noncanonical amino acids (ncAAs) to create semisynthetic organisms for both biochemical and biomedical applications. However, exogenous feeding of chemically synthesized ncAAs at high concentrations is required to compensate for the inefficient cellular uptake and incorporation of these components into proteins, especially in the case of eukaryotic cells and multicellular organisms. To generate organisms capable of autonomously biosynthesizing an ncAA and incorporating it into proteins, we have engineered a metabolic pathway for the synthesis of O-methyltyrosine (OMeY).

The Structure of the PEX4-PEX22 Peroxin Complex-Insights Into Ubiquitination at the Peroxisomal Membrane.

Peroxisomes are eukaryotic organelles that sequester critical oxidative reactions and process the resulting reactive oxygen species into less toxic byproducts. Peroxisome function and formation are coordinated by peroxins (PEX proteins) that guide peroxisome biogenesis and division and shuttle proteins into the lumen and membrane of the organelle. Despite the importance of peroxins in plant metabolism and development, no plant peroxin structures have been reported.

The crystal structure of DynF from the dynemicin-biosynthesis pathway of Micromonospora chersina.

Dynemicin is an enediyne natural product from Micromonospora chersina ATCC53710. Access to the biosynthetic gene cluster of dynemicin has enabled the in vitro study of gene products within the cluster to decipher their roles in assembling this unique molecule. This paper reports the crystal structure of DynF, the gene product of one of the genes within the biosynthetic gene cluster of dynemicin.

Structure and Function of a Dual Reductase-Dehydratase Enzyme System Involved in -Terphenyl Biosynthesis.

We report the identification of the gene cluster responsible for the formation of the -terphenyl derivatives terfestatins B and C and echoside B from the Appalachian strain RM-5-8. We characterize the function of TerB/C, catalysts that work together as a dual enzyme system in the biosynthesis of natural terphenyls. TerB acts as a reductase and TerC as a dehydratase to enable the conversion of polyporic acid to a terphenyl triol intermediate.

Structural characterization of DynU16, a START/Bet v1-like protein involved in dynemicin biosynthesis.

The 1.5 Å resolution crystal structure of DynU16, a protein identified in the dynemicin-biosynthetic gene cluster, is reported. The structure adopts a di-domain helix-grip fold with a uniquely positioned open cavity connecting the domains.

Moving beyond static snapshots: Protein dynamics and the Protein Data Bank.

Proteins are the molecular machines of living systems. Their dynamics are an intrinsic part of their evolutionary selection in carrying out their biological functions. Although the dynamics are more difficult to observe than a static, average structure, we are beginning to observe these dynamics and form sound mechanistic connections between structure, dynamics, and function.

A collagen glucosyltransferase drives lung adenocarcinoma progression in mice.

Cancer cells are a major source of enzymes that modify collagen to create a stiff, fibrotic tumor stroma. High collagen lysyl hydroxylase 2 (LH2) expression promotes metastasis and is correlated with shorter survival in lung adenocarcinoma (LUAD) and other tumor types. LH2 hydroxylates lysine (Lys) residues on fibrillar collagen's amino- and carboxy-terminal telopeptides to create stable collagen cross-links.

Molecular-replacement phasing using predicted protein structures from .

The phase problem in X-ray crystallography arises from the fact that only the intensities, and not the phases, of the diffracting electromagnetic waves are measured directly. Molecular replacement can often estimate the relative phases of reflections starting with those derived from a template structure, which is usually a previously solved structure of a similar protein. The key factor in the success of molecular replacement is finding a good template structure.

The crystal structure of AbsH3: A putative flavin adenine dinucleotide-dependent reductase in the abyssomicin biosynthesis pathway.

Natural products and natural product-derived compounds have been widely used for pharmaceuticals for many years, and the search for new natural products that may have interesting activity is ongoing. Abyssomicins are natural product molecules that have antibiotic activity via inhibition of the folate synthesis pathway in microbiota. These compounds also appear to undergo a required [4 + 2] cycloaddition in their biosynthetic pathway.