Chromatin is the complex assembly of nucleic acids and proteins that makes up the physiological form of the eukaryotic genome. The nucleosome is the fundamental repeating unit of chromatin, and is composed of ∼147 bp of DNA wrapped around a histone octamer formed by two copies of each core histone: H2A, H2B, H3 and H4. Prior to nucleosome assembly, and during histone eviction, histones are typically assembled into soluble H2A/H2B dimers and H3/H4 dimers and tetramers. A multitude of factors interact with soluble histone dimers and tetramers, including chaperones, importins, histone-modifying enzymes and chromatin-remodeling enzymes. It is still unclear how many of these proteins recognize soluble histones; therefore, there is a need for new structural tools to study non-nucleosomal histones. Here, a single-chain, tailless Xenopus H2A/H2B dimer was created by directly fusing the C-terminus of H2B to the N-terminus of H2A. It is shown that this construct (termed scH2BH2A) is readily expressed in bacteria and can be purified under non-denaturing conditions. A 1.31 Å resolution crystal structure of scH2BH2A shows that it adopts a conformation that is nearly identical to that of nucleosomal H2A/H2B. This new tool is likely to facilitate future structural studies of many H2A/H2B-interacting proteins.

Rice AKR in the apo structure reveals the ordered open conformation and its key residues which form the substrate channel wall and determine its substrate preference for straight-chain aldehydes.

From solutions of prehnitene and the ternary halides (SnCl)[MCl4] (M = Al, Ga) in chloro­benzene, the new cationic SnII–π-arene complexes catena-poly[[chlorido­aluminate(III)]-tri-μ-chlorido-4':1κ2Cl,1:2κ4Cl-[(η6-1,2,3,4-tetra­meth­yl­benzene)­tin(II)]-di-μ-chlorido-2:3κ4Cl-[(η6-1,2,3,4-tetra­methyl­benzene)­tin(II)]-di-μ-chlorido-3:4κ4Cl-[chlorido­aluminate(III)]-μ-chlorido-4:1'κ2Cl], [Al2Sn2Cl10(C10H14)2]n, (1) and catena-poly[[chlorido­gallate(III)]-tri-μ-chlor­ido-4':1κ2Cl,1:2κ4Cl-[(η6-1,2,3,4-tetra­methyl­benzene)­tin(II)]-di-μ-chlorido-2:3κ4Cl-[(η6-1,2,3,4-tetra­methyl­benzene)­tin(II)]-di-μ-chlorido-3:4κ4Cl-[chlor­ido­gallate(III)]-μ-chlorido-4:1'κ2Cl], [Ga2Sn2Cl10(C10H14)2]n, (2), were isolated. In these first main-group metal–prehnitene complexes, the distorted η6 arene π-bonding to the tin atoms of the Sn2Cl22+ moieties in the centre of [{1,2,3,4-(CH3)4C6H2}2Sn2Cl2][MCl4]2 repeating units (site symmetry overline{1}) is characterized by: (i) a significant ring slippage of ca 0.4 Å indicated by the dispersion of Sn—C distances [1: 2.881 (2)–3.216 (2) Å; 2: 2.891 (3)–3.214 (3) Å]; (ii) the non-methyl-substituted arene C atoms positioned closest to the SnII central atom; (iii) a pronounced tilt of the plane of the arene ligand against the plane of the central (Sn2Cl2)2+ four-membered ring species [1: 15.59 (11)°, 2: 15.69 (9)°]; (iv) metal–arene bonding of medium strength as illustrated by application of the bond-valence method in an indirect manner, defining the π-arene bonding inter­action of the SnII central atoms as s(SnII—arene) = 2 − Σs(SnII—Cl), that gives s(SnII—arene) = 0.37 and 0.38 valence units for the aluminate and the gallate, respectively, indicating that comparatively strong main-group metal–arene bonding is present and in line with the expectation that [AlCl4]− is the slightly weaker coordinating anion as compared to [GaCl4]−.

The title compound, hexa­kis­(2-methyl-1H-imidazol-3-ium) hepta­molybdate 2-methyl-1H-imidazole disolvate dihydrate, (C4H7N2)6[Mo7O24]·2C4H6N2·2H2O, was prepared from 2-methyl­imidazole and ammonium hepta­molybdate tetra­hydrate in acid solution. The [Mo7O24]6− hepta­molybdate cluster anion is accompanied by six protonated (C4H7N2)+ 2-methyl­imidazolium cations, two neutral C4H6N2 2-methyl­imidazole mol­ecules and two water mol­ecules of crystallization. The cluster consists of seven distorted MoO6 octa­hedra sharing edges or vertices. In the crystal, the components are linked by N—H⋯N, N—H⋯O, O—H⋯O, N—H⋯(O,O) and O—H⋯(O,O) hydrogen bonds, generating a three-dimensional network. Weak C—H⋯O inter­actions consolidate the packing.

The title tetra­nuclear copper complex, [Cu4Cl6O(C6H9N3O3)4] or [Cu4Cl6O­(MET)4] [MET is 1-(2-hy­droxy­eth­yl)-2-methyl-5-nitro-1H-imidazole or metronidazole], contains a tetra­hedral arrangement of copper(II) ions. Each copper atom is also linked to the other three copper atoms in the tetra­hedron via bridging chloride ions. A fifth coordination position on each metal atom is occupied by a nitro­gen atom of the monodentate MET ligand. The result is a distorted CuCl3NO trigonal–bipyramidal coordination polyhedron with the axial positions occupied by oxygen and nitro­gen atoms. The extended structure displays O—H⋯O hydrogen bonding, as well as unusual short O⋯N inter­actions [2.775 (4) Å] between the nitro groups of adjacent clusters that are oriented perpendicular to each other. The scattering contribution of disordered water and methanol solvent mol­ecules was removed using the SQUEEZE procedure [Spek (2015). Acta Cryst. C71, 9–16] in PLATON [Spek (2009). Acta Cryst. D65, 148–155].

The isostructural title compounds, poly[piperazin-1-ium [di-μ-bromido-caesium]], {(C4H11N2)[CsBr2]}n, and poly[piperazin-1-ium [di-μ-bromido-rubidium]], {(C4H11N2)[RbBr2]}n, contain singly-protonated piperazin-1-ium cations and unusual ABr6 (A = Cs or Rb) trigonal prisms. The prisms are linked into a distinctive `curtain wall' arrangement propagating in the (010) plane by face and edge sharing. In each case, a network of N—H⋯N, N—H⋯Br and N—H⋯(Br,Br) hydrogen bonds consolidates the structure.

Reaction of 2-(anthracen-9-yl)phenol (HOPhAn, 1) with divalent Yb[N(SiMe3)2]2·2THF in THF–toluene mixtures affords the mixed-valence YbII–YbIII dimer {[2-(anthracen-9-yl)phenolato-κO]bis­(tetra­hydro­furan)­ytterbium(III)}-tris­[μ-2-(anthracen-9-yl)phenolato]-κ4O:O;κO:1,2-η,κO-{[2-(anthracen-9-yl)phenolato-κO]ytterbium(II)} toluene tris­olvate, [Yb2(C20H13O)5(C4H8O)2]·3C7H7 or [YbIII(THF)2(OPhAn)](μ-OPhAn)3[YbII(OPhAn)]·3C7H7 (2), as the major product. It crystallized as a toluene tris­olvate. The Yb—O bond lengths in the crystal structure of this dimer clearly identify the YbII and YbIII centres. Inter­estingly, the formally four-coordinate YbII centre shows a close contact with one anthracene C—C bond of a bridging OPhAn ligand, bringing the formal coordination number to five.

Twelve 4-(4-meth­oxy­phen­yl)piperazin-1-ium salts containing organic anions have been prepared and structurally characterized. The monohydrated benzoate, 4-fluoro­benzoate, 4-chloro­benzoate and 4-bromo­benzoate salts, C11H17N2O+·C7H5O2−·H2O (I), C11H17N2O+·C7H4FO2−·H2O (II), C11H17N2O+·C7H4ClO2−·H2O (III), and C11H17N2O+·C7H4BrO2−·H2O (IV), respectively, are isomorphous and all exhibit disorder in the 4-meth­oxy­phenyl unit: the components are linked by N—H⋯O and O—H⋯O hydrogen bond to form chains of rings. The unsolvated 2-hy­droxy­benzoate, pyridine-3-carboxyl­ate and 2-hy­droxy-3,5-di­nitro­benzoate salts, C11H17N2O+·C7H5O3− (V), C11H17N2O+·C6H4NO2− (VI) and C11H17N2O+·C7H3N2O7− (VII), respectively, are all fully ordered: the components of (V) are linked by multiple N—H⋯O hydrogen bonds to form a chain of rings; those of (VI) are linked into a three-dimensional framework by a combination of N—H⋯O, C—H⋯O and C—H⋯N hydrogen bonds and those of (VII), where the anion has a structure reminiscent of the picrate anion, are linked into a three-dimensional array by N—H⋯O and C—H⋯O hydrogen bonds. The hydrogensuccinate and hydrogenfumarate salts, C11H17N2O+·C4H5O4− (VIII) and C11H17N2O+·C4H3O3− (IX), respectively, are isomorphous, and both exhibit disorder in the anionic component: N—H⋯O and O—H⋯O hydrogen bonds link the ions into sheets, which are further linked by C—H⋯π(arene) inter­actions. The anion of the hydrogenmaleate salt, C11H17N2O+·C4H3O3− (X), contains a very short and nearly symmetrical O⋯H⋯O hydrogen bond, and N—H⋯O hydrogen bonds link the anions into chains of rings. The ions in the tri­chloro­acetate salt, C11H17N2O+·C2Cl3O2− (XI), are linked into simple chains by N—H⋯O hydrogen bonds. In the hydrated chloranilate salt, 2C11H17N2O+·C6Cl2O42−·2H2O (XII), which crystallizes as a non-merohedral twin, the anion lies across a centre of inversion in space group P21/n, and a combination of N—H⋯O and O—H⋯O hydrogen bonds generates complex sheets. Comparisons are made with the structures of some related compounds.

In the title compound, (2,2'-bi­pyridine-κ2N,N')bis­(2-meth­oxy­ethyl xanthato-κS)zinc(II), [Zn(C4H7O2S2)2(C10H8N2)], the ZnII ion is coordinated to two N atoms of the 2,2'-bi­pyridine ligand and two S atoms from two 2-meth­oxy­ethyl xanthate ligands. The ZnII ion lies on a crystallographic twofold rotation axis and has distorted tetra­hedral coordination geometry. In the crystal, mol­ecules are linked by weak C—H⋯O hydrogen bonds, forming supramolecular chains propagating along the a-axis direction. Weak intra­molecular C—H⋯S hydrogen bonds are also observed. The inter­molecular contacts in the crystal were further analysed using Hirshfield surface analysis, which indicates that the most significant contacts are H⋯H (36.3%), followed by S⋯H/H⋯S (24.7%), C⋯H/H⋯C (15.1%), O⋯H/H⋯O (14.4%), N⋯H/H⋯N (4.1%) and C⋯C (2.9%).

The new heterometallic complex, aqua-1κO-bis­(μ2-2-imino­methyl-6-meth­oxy­phenolato-1κ2O1,O6:2κ2O1,N)bis­(thio­cyanato-1κN)calcium(II)copper(II), [CaCu(C8H8NO2)2(NCS)2(H2O)], has been synthesized using a one-pot reaction of copper powder, calcium oxide, o-vanillin and ammonium thio­cyanate in methanol under ambient conditions. The Schiff base ligand (C8H9NO2) is generated in situ from the condensation of o-vanillin and ammonia, which is released from the initial NH4SCN. The title compound consists of a discrete binuclear mol­ecule with a {Cu(μ-O)2Ca} core, in which the Cu⋯Ca distance is 3.4275 (6) Å. The coordination geometries of the four-coordinate copper atom in the [CuN2O2] chromophore and the seven-coordinate calcium atom in the [CaO5N2] chromophore can be described as distorted square planar and penta­gonal bipyramidal, respectively. In the crystal, O—H⋯S hydrogen bonds between the coordinating water mol­ecules and thio­cyanate groups form a supra­molecular chain with a zigzag-shaped calcium skeleton.

The title crystal structure is assembled from the superposition of two mol­ecular structures, (E)-1-(5-chloro­thio­phen-2-yl)-3-(3-methyl­thio­phen-2-yl)prop-2-en-1-one, C12H9ClOS2 (93%), and (Z)-1-(5-chloro­thio­phen-2-yl)-3-(3-methyl­thio­phen-2-yl)prop-1-en-1-ol, C12H11ClOS2 (7%), 0.93C12H9ClOS2·0.07C12H11ClOS2. Both were obtained from the reaction of 3-methyl­thio­phene-2-carbaldehyde and 1-(5-chloro­thio­phen-2-yl)ethanone. In the extended structure of the major chalcone component, mol­ecules are linked by a combination of C—H⋯O/S, Cl⋯Cl, Cl⋯π and π–π inter­actions, leading to a compact three-dimensional supra­molecular assembly.

A one-dimensional nickel(II) coordination polymer with the mixed ligands 6-fluoro­nicotinate (6-Fnic) and 4,4'-bi­pyridine (4,4'-bpy), namely, catena-poly[[di­aqua­bis­(6-fluoro­pyridine-3-carboxyl­ato-κO)nickel(II)]-μ-4,4'-bi­pyri­dine-κ2N:N'] trihydrate], {[Ni(6-Fnic)2(4,4'-bpy)(H2O)2]·3H2O}n, (1), was prepared by the reaction of nickel(II) sulfate hepta­hydrate, 6-fluoro­nicotinic acid (C6H4FNO2) and 4,4'-bi­pyridine (C10H8N2) in a mixture of water and ethanol. The nickel(II) ion in 1 is octa­hedrally coordinated by the O atoms of two water mol­ecules, two O atoms from O-monodentate 6-fluoro­nicotinate ligands and two N atoms from bridging 4,4'-bi­pyridine ligands, forming a trans isomer. The bridging 4,4'-bi­pyridine ligands connect symmetry-related nickel(II) ions into infinite one-dimensional polymeric chains running in the [1overline{1}0] direction. In the extended structure of 1, the polymeric chains and lattice water mol­ecules are connected into a three-dimensional hydrogen-bonded network via strong O—H⋯O and O—H⋯N hydrogen bonds, leading to the formation of distinct hydrogen-bond ring motifs: octa­meric R88(24) and hexa­meric R86(16) loops.

The syntheses and crystal structures of three mol­ecular salts of protonated 3,4-di­amino­benzoic acid, viz. 2-amino-5-carb­oxy­anilinium chloride, C7H9N2O2+·Cl−, (I), 2-amino-5-carb­oxy­anilinium bromide, C7H9N2O2+·Br−, (II), and 2-amino-5-carb­oxy­anilinium nitrate monohydrate, C7H9N2O2+·NO3−·H2O, (III), are described. The cation is protonated at the meta-N atom (with respect to the carb­oxy group) in each case. In the crystal of (I), carb­oxy­lic acid inversion dimers linked by pairwise O—H⋯O hydrogen bonds are seen and each N—H group forms a hydrogen bond to a chloride ion to result in (100) undulating layers of chloride ions bridged by the inversion dimers into a three-dimensional network. The extended structure of (II) features O—H⋯Br, N—H⋯Br and N—H⋯O hydrogen bonds: the last of these generates C(7) chains of cations. Overall, the packing in (II) features undulating (100) sheets of bromide ions alternating with the organic cations. Inter­molecular inter­actions in the crystal of (III) include O—H⋯O, O—H⋯(O,O), N—H⋯O, N—H⋯N and O—H⋯N links. The cations are linked into (001) sheets, and the nitrate ions and water mol­ecules form undulating chains. Taken together, alternating (001) slabs of organic cations plus anions/water mol­ecules result. Hirshfeld surfaces and fingerprint plots were generated to give further insight into the inter­molecular inter­actions in these structures. The crystal used for the data collection of (II) was twinned by rotation about [100] in reciprocal space in a 0.4896 (15):0.5104 (15) ratio.

The mechanism of formation of residual strain in crystals with a damaged surface has been studied by transmission electron microscopy in GaAs wafers ground with sandpaper. The samples showed a dislocation network located near the sample surface penetrating to a depth of a few micrometres, comparable to the size of abrasive particles used for the treatment, and no other types of defects were observed. A simple model for the formation of a compressive strain induced by the dislocation network in the damaged layer is proposed, in satisfactory agreement with the measured strain. The strain is generated by the formation of dislocation half-loops at the crystal surface, having the same component of the Burgers vectors parallel to the surface of the crystal. This is equivalent to the insertion of extra half-planes from the crystal surface to the depth of the damaged zone. This model can be generalized for other crystal structures. An approximate calculation of the strain generated from the observed dislocation distribution in the sample agrees with the proposed model and permits the conclusion that this mechanism is in general sufficient to explain the observed compressive strain, without the need to consider other types of defects.

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.

Aminoacyl-tRNA synthetases (ARSs) play essential roles in protein biosynthesis as well as in other cellular processes, often using evolutionarily acquired domains. For possible cooperativity and synergistic effects, nine ARSs assemble into the multi-tRNA synthetase complex (MSC) with three scaffold proteins: aminoacyl-tRNA synthetase complex-interacting multifunctional proteins 1, 2 and 3 (AIMP1, AIMP2 and AIMP3). X-ray crystallographic methods were implemented in order to determine the structure of a ternary subcomplex of the MSC comprising aspartyl-tRNA synthetase (DRS) and two glutathione S-transferase (GST) domains from AIMP2 and glutamyl-prolyl-tRNA synthetase (AIMP2GST and EPRSGST, respectively). While AIMP2GST and EPRSGST interact via conventional GST heterodimerization, DRS strongly interacts with AIMP2GST via hydrogen bonds between the α7–β9 loop of DRS and the β2–α2 loop of AIMP2GST, where Ser156 of AIMP2GST is essential for the assembly. Structural analyses of DRS–AIMP2GST–EPRSGST reveal its pivotal architecture in the MSC and provide valuable insights into the overall assembly and conditionally required disassembly of the MSC.

A three-dimensional hydrogen-bonded network based on a rare mok topology has been constructed using an organic molecule synthesized in the solid state. The molecule is obtained using a supramolecular protecting-group strategy that is applied to a solid-state [2+2] photodimerization. The photodimerization affords a novel head-to-head cyclo­butane product. The cyclo­butane possesses tetrahedrally disposed cis-hydrogen-bond donor (phenolic) and cis-hydrogen-bond acceptor (pyridyl) groups. The product self-assembles in the solid state to form a mok network that exhibits twofold interpenetration. The cyclo­butane adopts different conformations to provide combinations of hydrogen-bond donor and acceptor sites to conform to the structural requirements of the mok net.

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.

MICAL is an oxidoreductase that participates in cytoskeleton reorganization via actin disassembly in the presence of NADPH. Although three MICALs (MICAL1, MICAL2 and MICAL3) have been identified in mammals, only the structure of mouse MICAL1 has been reported. Here, the first crystal structure of human MICAL3, which contains the flavin-containing monooxygenase (FMO) and calponin-homology (CH) domains, is reported. MICAL3 has an FAD/NADP-binding Rossmann-fold domain for mono­oxygenase activity like MICAL1. The FMO and CH domains of both MICAL3 and MICAL1 are highly similar in structure, but superimposition of the two structures shows a different relative position of the CH domain in the asymmetric unit. Based on kinetic analyses, the catalytic efficiency of MICAL3 dramatically increased on adding F-actin only when the CH domain was available. However, this did not occur when two residues, Glu213 and Arg530, were mutated in the FMO and CH domains, respectively. Overall, MICAL3 is structurally highly similar to MICAL1, which suggests that they may adopt the same catalytic mechanism, but the difference in the relative position of the CH domain produces a difference in F-actin substrate specificity.

Co-crystallization is a phenomenon widely employed to enhance the physio-chemical and biological properties of active pharmaceutical ingredients (APIs). Exemestane, or 6-methyl­ideneandrosta-1,4-diene-3,17-dione, is an anabolic steroid used as an irreversible steroidal aromatase inhibitor, which is in clinical use to treat breast cancer. The present study deals with the synthesis of co-crystals of exemestane with thio­urea by liquid-assisted grinding. The purity and homogeneity of the exemestane–thio­urea (1:1) co-crystal were confirmed by single-crystal X-ray diffraction followed by thermal stability analysis on the basis of differential scanning calorimetry and thermogravimetric analysis. Detailed geometric analysis of the co-crystal demonstrated that a 1:1 co-crystal stoichiometry is sustained by N—H⋯O hydrogen bonding between the amine (NH2) groups of thio­urea and the carbonyl group of exemestane. The synthesized co-crystal exhibited potent urease inhibition activity in vitro (IC50 = 3.86 ± 0.31 µg ml−1) compared with the API (exemestane), which was found to be inactive, and the co-former (thio­urea) (IC50 = 21.0 ± 1.25 µg ml−1), which is also an established tested standard for urease inhibition assays in vitro. The promising results of the present study highlight the significance of co-crystallization as a crystal engineering tool to improve the efficacy of pharmaceutical ingredients. Furthermore, the role of various hydrogen bonds in the crystal stability is successfully analysed quantitatively using Hirshfeld surface analysis.

In chemistry, stereochemically active lone pairs are typically described as an important non-bonding effect, and recent interest has centred on understanding the derived effect of lone pair expression on physical properties such as thermal conductivity. To manipulate such properties, it is essential to understand the conditions that lead to lone pair expression and provide a quantitative chemical description of their identity to allow comparison between systems. Here, density functional theory calculations are used first to establish the presence of stereochemically active lone pairs on antimony in the archetypical chalcogenide MnSb2O4. The lone pairs are formed through a similar mechanism to those in binary post-transition metal compounds in an oxidation state of two less than their main group number [e.g. Pb(II) and Sb(III)], where the degree of orbital interaction (covalency) determines the expression of the lone pair. In MnSb2O4 the Sb lone pairs interact through a void space in the crystal structure, and their their mutual repulsion is minimized by introducing a deflection angle. This angle increases significantly with decreasing Sb—Sb distance introduced by simulating high pressure, thus showing the highly destabilizing nature of the lone pair interactions. Analysis of the chemical bonding in MnSb2O4 shows that it is dominated by polar covalent interactions with significant contributions both from charge accumulation in the bonding regions and from charge transfer. A database search of related ternary chalcogenide structures shows that, for structures with a lone pair (SbX3 units), the degree of lone pair expression is largely determined by whether the antimony–chalcogen units are connected or not, suggesting a cooperative effect. Isolated SbX3 units have larger X—Sb—X bond angles and therefore weaker lone pair expression than connected units. Since increased lone pair expression is equivalent to an increased orbital interaction (covalent bonding), which typically leads to increased heat conduction, this can explain the previously established correlation between larger bond angles and lower thermal conductivity. Thus, it appears that for these chalcogenides, lone pair expression and thermal conductivity may be related through the degree of covalency of the system.

Copper-containing nitrite reductases (CuNiRs) are found in all three kingdoms of life and play a major role in the denitrification branch of the global nitro­gen cycle where nitrate is used in place of di­oxy­gen as an electron acceptor in respiratory energy metabolism. Several C- and N-terminal redox domain tethered CuNiRs have been identified and structurally characterized during the last decade. Our understanding of the role of tethered domains in these new classes of three-domain CuNiRs, where an extra cytochrome or cupredoxin domain is tethered to the catalytic two-domain CuNiRs, has remained limited. This is further compounded by a complete lack of substrate-bound structures for these tethered CuNiRs. There is still no substrate-bound structure for any of the as-isolated wild-type tethered enzymes. Here, structures of nitrite and product-bound states from a nitrite-soaked crystal of the N-terminal cupredoxin-tethered enzyme from the Hyphomicrobium denitrificans strain 1NES1 (Hd1NES1NiR) are provided. These, together with the as-isolated structure of the same species, provide clear evidence for the role of the N-terminal peptide bearing the conserved His27 in water-mediated anchoring of the substrate at the catalytic T2Cu site. Our data indicate a more complex role of tethering than the intuitive advantage for a partner-protein electron-transfer complex by narrowing the conformational search in such a combined system.

Apoptosis is a crucial process by which multicellular organisms control tissue growth, removal and inflammation. Disruption of the normal apoptotic function is often observed in cancer, where cell death is avoided by the overexpression of anti-apoptotic proteins of the Bcl-2 (B-cell lymphoma 2) family, including Mcl-1 (myeloid cell leukaemia 1). This makes Mcl-1 a potential target for drug therapy, through which normal apoptosis may be restored by inhibiting the protective function of Mcl-1. Here, the discovery and biophysical properties of an anti-Mcl-1 antibody fragment are described and the utility of both the scFv and Fab are demonstrated in generating an Mcl-1 crystal system amenable to iterative structure-guided drug design.

The refinement of biomolecular crystallographic models relies on geometric restraints to help to address the paucity of experimental data typical in these experiments. Limitations in these restraints can degrade the quality of the resulting atomic models. Here, an integration of the full all-atom Amber molecular-dynamics force field into Phenix crystallographic refinement is presented, which enables more complete modeling of biomolecular chemistry. The advantages of the force field include a carefully derived set of torsion-angle potentials, an extensive and flexible set of atom types, Lennard–Jones treatment of nonbonded interactions and a full treatment of crystalline electrostatics. The new combined method was tested against conventional geometry restraints for over 22 000 protein structures. Structures refined with the new method show substantially improved model quality. On average, Ramachandran and rotamer scores are somewhat better, clashscores and MolProbity scores are significantly improved, and the modeling of electrostatics leads to structures that exhibit more, and more correct, hydrogen bonds than those refined using traditional geometry restraints. In general it is found that model improvements are greatest at lower resolutions, prompting plans to add the Amber target function to real-space refinement for use in electron cryo-microscopy. This work opens the door to the future development of more advanced applications such as Amber-based ensemble refinement, quantum-mechanical representation of active sites and improved geometric restraints for simulated annealing.

Noncrystallographic symmetry (NCS) averaging following molecular-replacement phasing is generally the major technique used to solve a structure with several molecules in one asymmetric unit, such as a spherical icosahedral viral particle. As an alternative method to NCS averaging, a new approach to optimize or to refine the electron density directly under NCS constraints is proposed. This method has the same effect as the conventional NCS-averaging method but does not include the process of Fourier synthesis to generate the electron density from amplitudes and the corresponding phases. It has great merit for the solution of structures with limited data that are either twinned or incomplete at low resolution. This method was applied to the case of the T = 1 shell-domain subviral particle of Penaeus vannamei nodavirus with data affected by twinning using the REFMAC5 refinement software.

Tryptophan synthase catalyzes the last two steps of tryptophan biosynthesis in plants, fungi and bacteria. It consists of two protein chains, designated α and β, encoded by trpA and trpB genes, that function as an αββα complex. Structural and functional features of tryptophan synthase have been extensively studied, explaining the roles of individual residues in the two active sites in catalysis and allosteric regulation. TrpA serves as a model for protein-folding studies. In 1969, Jackson and Yanofsky observed that the typically monomeric TrpA forms a small population of dimers. Dimerization was postulated to take place through an exchange of structural elements of the monomeric chains, a phenomenon later termed 3D domain swapping. The structural details of the TrpA dimer have remained unknown. Here, the crystal structure of the Streptococcus pneumoniae TrpA homodimer is reported, demonstrating 3D domain swapping in a TIM-barrel fold for the first time. The N-terminal domain comprising the H0–S1–H1–S2 elements is exchanged, while the hinge region corresponds to loop L2 linking strand S2 to helix H2'. The structural elements S2 and L2 carry the catalytic residues Glu52 and Asp63. As the S2 element is part of the swapped domain, the architecture of the catalytic apparatus in the dimer is recreated from two protein chains. The homodimer interface overlaps with the α–β interface of the tryptophan synthase αββα heterotetramer, suggesting that the 3D domain-swapped dimer cannot form a complex with the β subunit. In the crystal, the dimers assemble into a decamer comprising two pentameric rings.

Fragment-based molecular-replacement methods can solve a macromolecular structure quasi-ab initio. ARCIMBOLDO, using a common secondary-structure or tertiary-structure template or a library of folds, locates these with Phaser and reveals the rest of the structure by density modification and autotracing in SHELXE. The latter stage is challenging when dealing with diffraction data at lower resolution, low solvent content, high β-sheet composition or situations in which the initial fragments represent a low fraction of the total scattering or where their accuracy is low. SEQUENCE SLIDER aims to overcome these complications by extending the initial polyalanine fragment with side chains in a multisolution framework. Its use is illustrated on test cases and previously unknown structures. The selection and order of fragments to be extended follows the decrease in log-likelihood gain (LLG) calculated with Phaser upon the omission of each single fragment. When the starting substructure is derived from a remote homolog, sequence assignment to fragments is restricted by the original alignment. Otherwise, the secondary-structure prediction is matched to that found in fragments and traces. Sequence hypotheses are trialled in a brute-force approach through side-chain building and refinement. Scoring the refined models through their LLG in Phaser may allow discrimination of the correct sequence or filter the best partial structures for further density modification and autotracing. The default limits for the number of models to pursue are hardware dependent. In its most economic implementation, suitable for a single laptop, the main-chain trace is extended as polyserine rather than trialling models with different sequence assignments, which requires a grid or multicore machine. SEQUENCE SLIDER has been instrumental in solving two novel structures: that of MltC from 2.7 Å resolution data and that of a pneumococcal lipoprotein with 638 residues and 35% solvent content.

Oxidation states of individual metal atoms within a metalloprotein can be assigned by examining X-ray absorption edges, which shift to higher energy for progressively more positive valence numbers. Indeed, X-ray crystallography is well suited for such a measurement, owing to its ability to spatially resolve the scattering contributions of individual metal atoms that have distinct electronic environments contributing to protein function. However, as the magnitude of the shift is quite small, about +2 eV per valence state for iron, it has only been possible to measure the effect when performed with monochromated X-ray sources at synchrotron facilities with energy resolutions in the range 2–3 × 10−4 (ΔE/E). This paper tests whether X-ray free-electron laser (XFEL) pulses, which have a broader bandpass (ΔE/E = 3 × 10−3) when used without a monochromator, might also be useful for such studies. The program nanoBragg is used to simulate serial femtosecond crystallography (SFX) diffraction images with sufficient granularity to model the XFEL spectrum, the crystal mosaicity and the wavelength-dependent anomalous scattering factors contributed by two differently charged iron centers in the 110-amino-acid protein, ferredoxin. Bayesian methods are then used to deduce, from the simulated data, the most likely X-ray absorption curves for each metal atom in the protein, which agree well with the curves chosen for the simulation. The data analysis relies critically on the ability to measure the incident spectrum for each pulse, and also on the nanoBragg simulator to predict the size, shape and intensity profile of Bragg spots based on an underlying physical model that includes the absorption curves, which are then modified to produce the best agreement with the simulated data. This inference methodology potentially enables the use of SFX diffraction for the study of metalloenzyme mechanisms and, in general, offers a more detailed approach to Bragg spot data reduction.

The information gained by making a measurement, termed the Kullback–Leibler divergence, assesses how much more precisely the true quantity is known after the measurement was made (the posterior probability distribution) than before (the prior probability distribution). It provides an upper bound for the contribution that an observation can make to the total likelihood score in likelihood-based crystallographic algorithms. This makes information gain a natural criterion for deciding which data can legitimately be omitted from likelihood calculations. Many existing methods use an approximation for the effects of measurement error that breaks down for very weak and poorly measured data. For such methods a different (higher) information threshold is appropriate compared with methods that account well for even large measurement errors. Concerns are raised about a current trend to deposit data that have been corrected for anisotropy, sharpened and pruned without including the original unaltered measurements. If not checked, this trend will have serious consequences for the reuse of deposited data by those who hope to repeat calculations using improved new methods.

Strain tensor measurements are important for understanding elastic and plastic deformation, but full bulk strain tensor measurement techniques are still lacking, in particular for dynamic loading. Here, such a methodology is reported, combining imaging-based strain field mapping and simultaneous X-ray diffraction for four typical loading modes: one-dimensional strain/stress compression/tension. Strain field mapping resolves two in-plane principal strains, and X-ray diffraction analysis yields volumetric strain, and thus the out-of-plane principal strain. This methodology is validated against direct molecular dynamics simulations on nanocrystalline tantalum. This methodology can be implemented with simultaneous X-ray diffraction and digital image correlation in synchrotron radiation or free-electron laser experiments.

A method for reconstructing the three-dimensional grain structure from data collected with a recently introduced laboratory-based X-ray diffraction contrast tomography system is presented. Diffraction contrast patterns are recorded in Laue-focusing geometry. The diffraction geometry exposes shape information within recorded diffraction spots. In order to yield the three-dimensional crystallographic microstructure, diffraction spots are extracted and fed into a reconstruction scheme. The scheme successively traverses and refines solution space until a reasonable reconstruction is reached. This unique reconstruction approach produces results efficiently and fast for well suited samples.

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.

Silicon nanowire-based sensors find many applications in micro- and nano-electromechanical systems, thanks to their unique characteristics of flexibility and strength that emerge at the nanoscale. This work is the first study of this class of micro- and nano-fabricated silicon-based structures adopting the scanning X-ray diffraction microscopy technique for mapping the in-plane crystalline strain (∊044) and tilt of a device which includes pillars with suspended nanowires on a substrate. It is shown how the micro- and nanostructures of this new type of nanowire system are influenced by critical steps of the fabrication process, such as electron-beam lithography and deep reactive ion etching. X-ray analysis performed on the 044 reflection shows a very low level of lattice strain (<0.00025 Δd/d) but a significant degree of lattice tilt (up to 0.214°). This work imparts new insights into the crystal structure of micro- and nanomaterial-based sensors, and their relationship with critical steps of the fabrication process.

The residual strain distribution has been measured as a function of depth in both top coat and bond coat in as-received and heat-treated air plasma sprayed thermal barrier coating samples. High-energy synchrotron X-ray beams were used in transmission to produce full Debye–Scherrer rings whose non-circular aspect ratio gave the in-plane and out-of-plane strains far more efficiently than the sin2ψ method. The residual strain in the bond coat is found to be tensile and the strain in the β phase of the as-received sample was measured. The residual strains observed in the top coat were generally compressive (increasing towards the interface), with two kinds of nonlinear trend. These was a `jump' feature near the interface, and in some cases there was another `jump' feature near the surface. It is shown how these trend differences can be correlated to cracks in the coating.

BornAgain is a free and open-source multi-platform software framework for simulating and fitting X-ray and neutron reflectometry, off-specular scattering, and grazing-incidence small-angle scattering (GISAS). This paper concentrates on GISAS. Support for reflectometry and off-specular scattering has been added more recently, is still under intense development and will be described in a later publication. BornAgain supports neutron polarization and magnetic scattering. Users can define sample and instrument models through Python scripting. A large subset of the functionality is also available through a graphical user interface. This paper describes the software in terms of the realized non-functional and functional requirements. The web site https://www.bornagainproject.org/ provides further documentation.

Molybdenum oxides and sulfides on various low-cost high-surface-area supports are excellent catalysts for several industrially relevant reactions. The surface layer structure of these materials is, however, difficult to characterize due to small and disordered MoOx domains. Here, it is shown how X-ray total scattering can be applied to gain insights into the structure through differential pair distribution function (d-PDF) analysis, where the scattering signal from the support material is subtracted to obtain structural information on the supported structure. MoOx catalysts supported on alumina nanoparticles and on zeolites are investigated, and it is shown that the structure of the hydrated molybdenum oxide layer is closely related to that of disordered and polydisperse polyoxometalates. By analysing the PDFs with a large number of automatically generated cluster structures, which are constructed in an iterative manner from known polyoxometalate clusters, information is derived on the structural motifs in supported MoOx.

An error in the article by Gao, Zhang, Zhu, Wu, Mo, Pan, Liu & Jiang [J. Appl. Cryst. (2019), 52, 637–642] is corrected.

Two methods for reconstructing intragranular strain fields are developed for scanning three-dimensional X-ray diffraction (3DXRD). The methods are compared with a third approach where voxels are reconstructed independently of their neighbours [Hayashi, Setoyama & Seno (2017). Mater. Sci. Forum, 905, 157–164]. The 3D strain field of a tin grain, located within a sample of approximately 70 grains, is analysed and compared across reconstruction methods. Implicit assumptions of sub-problem independence, made in the independent voxel reconstruction method, are demonstrated to introduce bias and reduce reconstruction accuracy. It is verified that the two proposed methods remedy these problems by taking the spatial properties of the inverse problem into account. Improvements in reconstruction quality achieved by the two proposed methods are further supported by reconstructions using synthetic diffraction data.

An online knowledge base on the alternate conformations adopted by main-chain and side-chain atoms in protein structures solved by X-ray crystallography is described.

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.

New fitting analyses of two-dimensional diffraction-spot shapes are demonstrated to evaluate strain, strain distribution and domain size in a crystalline ultra-thin film. The evaluations are displayed as residual and population maps as a function of strain or domain size.

Ba excess in LaBaGaO4 triggers ionic conductivity together with structural disorder. A direct correlation is found between the density functional theory model energy and the pair distribution function fit residual.

The distribution of plastic relaxation defects is studied using a nondestructive sub-micrometre X-ray diffraction scanning technique.

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.

A fast and exact algorithm to calculate the powder pair distribution function (PDF) for the case of periodic structures is presented. The algorithm especially improves X-ray and electron PDF calculations, and the handling of instrumental resolution functions.

The sasPDF method, an extension of the atomic pair distribution function (PDF) analysis to the small-angle scattering (SAS) regime, is presented. The method is applied to characterize the structure of nanoparticle assemblies with different levels of structural order.

A detailed theoretical and experimental comparison of dark-field electron holography (DFEH) and high-resolution X-ray diffraction (HRXRD) is performed. Both techniques are being applied to measure elastic strain in an array of transistors and the role of the geometric phase is emphasized.

The crystal structure of the organic pigment 2-monomethyl-quinacridone (Pigment Red 192, C21H14N2O2) was solved from X-ray powder diffraction data. The resulting average structure is described in space group Poverline 1, Z = 1 with the molecule on the inversion centre. The molecules are arranged in chains. The molecules, which have no inversion symmetry, show orientational head-to-tail disorder. In the average structure, the methyl group is disordered and found on both ends of the molecule with an occupancy of 0.5 each. The disorder and the local structure were investigated using various ordered structural models. All models were analysed by three approaches: Rietveld refinement, structure refinement to the pair distribution function (PDF) and lattice-energy minimization. All refinements converged well. The Rietveld refinement provided the average structure and gave no indication of a long-range ordering. The refinement to the PDF turned out to be very sensitive to small structural details, giving insight into the local structure. The lattice-energy minimizations revealed a significantly preferred local ordering of neighbouring molecules along the [0ar 11] direction. In conclusion, all methods indicate a statistical orientational disorder with a preferred parallel orientation of molecules in one direction. Additionally, electron diffraction revealed twinning and faint diffuse scattering.

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.