Structure solution of the Al69.2Cu20Cr10.8 ϕ phase

The stable ϕ phase that forms below ∼923 K around the Al69.2Cu20.0Cr10.8 composition was found to be hexagonal [P63, a = 11.045 (2), c = 12.688 (2) Å] and isostructural to the earlier reported Al6.2Cu2Re X phase [Samuha, Grushko & Meshi (2016). J. Alloys Compd. 670, 18–24]. Using the structural model of the latter, a successful Rietveld refinement of the XRD data for Al69.5Cu20.0Cr10.5 was performed. Both ϕ and X were found to be structurally related to the Al72.6Cu11.0Cr16.4 ζ phase [P63/m, a = 17.714, c = 12.591 Å; Sugiyama, Saito & Hiraga (2002). J. Alloys Compd. 342, 148–152], with a close lattice parameter c and a τ-times-larger lattice parameter a (τ is the golden mean). The structural relationship between ζ and ϕ was established on the basis of the similarity of their layered structures and common features. Additionally, the strong-reflections approach was successfully applied for the modeling of the ϕ phase based on the structural model of the ζ phase. The latter and the experimental structural model (retrieved following Rietveld refinement) were found to be essentially identical.

Crystallization and low-resolution structure solution of the SALM3–PTPσ synaptic adhesion complex

Synaptic adhesion molecules are major organizers of the neuronal network and play a crucial role in the regulation of synapse development and maintenance in the brain. Synaptic adhesion-like molecules (SALMs) and leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-PTPs) are adhesion protein families with established synaptic function. Dysfunction of several synaptic adhesion molecules has been linked to cognitive disorders such as autism spectrum disorders and schizophrenia. A recent study of the binding and complex structure of SALM3 and PTPσ using small-angle X-ray scattering revealed a 2:2 complex similar to that observed for the interaction of human SALM5 and PTPδ. However, the molecular structure of the SALM3–PTPσ complex remains to be determined beyond the small-angle X-ray scattering model. Here, the expression, purification, crystallization and initial 6.5 Å resolution structure of the mouse SALM3–PTPσ complex are reported, which further verifies the formation of a 2:2 trans-heterotetrameric complex similar to the crystal structure of human SALM5–PTPδ and validates the architecture of the previously reported small-angle scattering-based solution structure of the SALM3–PTPσ complex. Details of the protein expression and purification, crystal optimization trials, and the initial structure solution and data analysis are provided.

Towards the automatic crystal structure solution of nucleic acids: automated model building using the new CAB program

CAB, a recently described automated model-building (AMB) program, has been modified to work effectively with nucleic acids. To this end, several new algorithms have been introduced and the libraries have been updated. To reduce the input average phase error, ligand heavy atoms are now located before starting the CAB interpretation of the electron-density maps. Furthermore, alternative approaches are used depending on whether the ligands belong to the target or to the model chain used in the molecular-replacement step. Robust criteria are then applied to decide whether the AMB model is acceptable or whether it must be modified to fit prior information on the target structure. In the latter case, the model chains are rearranged to fit prior information on the target chains. Here, the performance of the new AMB program CAB applied to various nucleic acid structures is discussed. Other well documented programs such as Nautilus, ARP/wARP and phenix.autobuild were also applied and the experimental results are described.

Enhanced Refractive Index Sensing Performance Using Hydrothermally Prepared Tricomposite Nanoflower Structure of Ta2O5:Si:Graphite

We describe a tricomposite nanoflower structure based method to measure the trace amount of refractive index in aqueous solutions. It utilizes tantalum (v) oxide, silicon and graphite to fabricate the tricomposite nanostructures. The tricomposite nanoflower structures were prepared using hydrothermal method where the concentration of (x) of Si in Ta2O5 was varied while the concentration of graphite was kept constant. The concentration of Si in Ta2O5 was measured by Maxwell-Garnett model using volume filling factor 'f' (0≤f≤1) of Si in Ta2O5. The fabricated Ta2O5:Si:Graphite tricomposite nanoflower structures were characterized by SEM, XRD, UV-Vis, PL, FTIR characterization techniques. Then aqueous solution of varying refractive indices were prepared in the range 1.33-1.39 in the already prepared tricomposite nanoflower structure solution. The refractive index measurement were probed by measuring absorption spectra corresponding to each tricomposite nanoflower structures. The performance of the sensor was explored in terms of shift in peak absorption spectra, sensitivity and moreover the limit of detection. The sensor shows sensitivity and limit of detection of (156-260) nm/RIU and 5.14x10-3 RIU respectively. A linear declining of sensitivity was observed within the refractive index range. The sensor possesses a distinguished feature of using tricomposite nanoflower structure which is an efficient method for refractive index measurement.

Oxidation state variation in bis-calix[4]arene supported decametallic Mn clusters

The reaction of MnCl2·4H2O, H8L (2,2’-bis-p-tBu-calix[4]arene) and NEt3 in a dmf/MeOH solvent mixture results in the formation of a mixed valent decametallic cluster of formula [MnII6MnIII4(L)2(µ3-OH)4(µ-OH)4(MeOH)4(dmf)4(MeCN)2]·MeCN (3). Complex 3 crystallises in the monoclinic space group P21/n with the asymmetric unit comprising half of the compound. Structure solution reveals that the bis-calix[4]arene ligands are arranged such that one TBC[4] moiety in each has undergone inversion in order to accommodate a [MnIII4MnII6] metallic skeleton that describes three vertex-sharing [MnIII2MnII2] butterflies. The structure is closely related to the species [MnIII6MnII4(L)2(μ3-O)2(μ3-OH)2(μ-OMe)4(H2O)4(dmf)8]·4dmf (4), the major difference being the oxidation level of the Mn ions in the core of the compound. DFT calculations on the full structures reveal that replacing the MnIII ions in 4 for MnII ions in 3 results in a significant decrease in the magnitude of some antiferromagnetic exchange contributions, a switch from ferromagnetic to antiferromagnetic in others, and the loss of significant spin frustration.

Crystal structure of brigatinib Form A (Alunbrig®), C29H39ClN7O2P

The crystal structure of brigatinib Form A has been solved and refined using synchrotron X-ray powder diffraction data and optimized using density functional theory techniques. Brigatinib Form A crystallizes in space group P-1 (#2) with a = 9.59616(20), b = 10.9351(3), c = 14.9913(6) Å, α = 76.1210(13), β = 79.9082(11), γ = 74.0802(6)°, V = 1458.497(15) Å3, and Z = 2. Structure solution was complicated by the lowest cost factor solution having an unreasonable conformation of the dimethylphosphoryl group. The second-best structure yielded a better refinement. The crystal structure is characterized by alternating layers of aliphatic and aromatic portions of the molecules along the b-axis. Strong N–H⋯N hydrogen bonds link the molecules into pairs, with a graph set R2,2(8). There is a strong intramolecular N–H⋯O hydrogen bond to the phosphoryl group, which determines the orientation of this group. The powder pattern has been submitted to ICDD® for inclusion in the Powder Diffraction File™ (PDF®).

Experimental evidence for the benefits of higher X-ray energies for macromolecular crystallography

X-ray-induced radiation damage is a limiting factor for the macromolecular crystallographer and data must often be merged from many crystals to yield complete data sets for the structure solution of challenging samples. Increasing the X-ray energy beyond the typical 10–15 keV range promises to provide an extension of crystal lifetime via an increase in diffraction efficiency. To date, however, hardware limitations have negated any possible gains. Through the first use of a cadmium telluride EIGER2 detector and a beamline optimized for high-energy data collection, it is shown that at higher energies fewer crystals will be required to obtain complete data, as the diffracted intensity per unit dose increases by a factor of more than two between 12.4 and 25 keV. Additionally, these higher energy data can provide more information, as shown by a systematic increase in the high-resolution cutoff of the data collected. Taken together, these gains point to a high-energy future for synchrotron-based macromolecular crystallography.

MrParse: Finding homologues in the PDB and the EBI AlphaFold database for Molecular Replacement and more

Crystallographers have an array of search model options for structure solution by Molecular Replacement (MR). Well-established options of homologous experimental structures and regular secondary structure elements or motifs are increasingly supplemented by computational modelling. Such modelling may be carried out locally or use pre-calculated predictions retrieved from databases such as the EBI AlphaFold database. MrParse is a new pipeline to help streamline the decision process in MR by consolidating bioinformatic predictions in one place. When reflection data are provided, MrParse can rank any homologues found using eLLG which indicates the likelihood that a given search model will work in MR. In-built displays of predicted secondary structure, coiled-coil and transmembrane regions further inform the choice of MR protocol. MrParse can also identify and rank homologues in the EBI AlphaFold database, a function that will also interest other structural biologists and bioinformaticians.