Proteins Do Not Have Strong Spines After All

In this issue of Structure, Berkholz et al. show that the detailed backbone geometry of proteins depends on the local conformation and suggest how this information can be practically used in modeling and refining protein structures

Impact of synchrotron radiation on macromolecular crystallography: a personal view

This article, largely based on personal experiences of the authors, reviews the early history of the application of synchrotron radiation to structural biology, and particularly protein crystallography, to show the tremendous impact that this experimental innovation has had on these disciplines

N-{N-[2-(3,5-Difluoro­phenyl)acetyl]-(S)-alanyl}-(S)-phenyl­glycine tert-butyl ester (DAPT): an inhibitor of γ-secretase, revealing fine electronic and hydrogen-bonding features

The title compound, C23H26F2N2O4, is a dipeptidic inhibitor of γ-secretase, one of the enzymes involved in Alzheimer’s dis­ease. The mol­ecule adopts a compact conformation, without intra­molecular hydrogen bonds. In the crystal structure, one of the amide N atoms forms the only inter­molecular N—H⋯O hydrogen bond; the second amide N atom does not form hydrogen bonds. High-resolution synchrotron diffraction data permitted the unequivocal location and refinement without restraints of all H atoms, and the identification of the characteristic shift of the amide H atom engaged in the hydrogen bond from its ideal position, resulting in a more linear hydrogen bond. Significant residual densities for bonding electrons were revealed after the usual SHELXL refinement, and modeling of these features as additional inter­atomic scatterers (IAS) using the program PHENIX led to a significant decrease in the R factor from 0.0411 to 0.0325 and diminished the r.m.s. deviation level of noise in the final difference Fourier map from 0.063 to 0.037 e Å−3

Spermidine Synthase (SPDS) Undergoes Concerted Structural Rearrangements Upon Ligand Binding – A Case Study of the Two SPDS Isoforms From Arabidopsis thaliana

Spermidine synthases (SPDSs) catalyze the production of the linear triamine, spermidine, from putrescine. They utilize decarboxylated S-adenosylmethionine (dc-SAM), a universal cofactor of aminopropyltransferases, as a donor of the aminopropyl moiety. In this work, we describe crystal structures of two SPDS isoforms from Arabidopsis thaliana (AtSPDS1 and AtSPDS2). AtSPDS1 and AtSPDS2 are dimeric enzymes that share the fold of the polyamine biosynthesis proteins. Subunits of both isoforms present the characteristic two-domain structure. Smaller, N-terminal domain is built of the two β-sheets, while the C-terminal domain has a Rossmann fold-like topology. The catalytic cleft composed of two main compartments, the dc-SAM binding site and the polyamine groove, is created independently in each AtSPDS subunits at the domain interface. We also provide the structural details about the dc-SAM binding mode and the inhibition of SPDS by a potent competitive inhibitor, cyclohexylamine (CHA). CHA occupies the polyamine binding site of AtSPDS where it is bound at the bottom of the active site with the amine group placed analogously to the substrate. The crystallographic snapshots show in detail the structural rearrangements of AtSPDS1 and AtSPDS2 that are required to stabilize ligands within the active site. The concerted movements are observed in both compartments of the catalytic cleft, where three major parts significantly change their conformation. These are (i) the neighborhood of the glycine-rich region where aminopropyl moiety of dc-SAM is bound, (ii) the very flexible gate region with helix η6, which interacts with both, the adenine moiety of dc-SAM and the bound polyamine or inhibitor, and (iii) the N-terminal β-hairpin, that limits the putrescine binding grove at the bottom of the catalytic site

SU(2) Cosmological Solitons

We present a class of numerical solutions to the SU(2) nonlinear $\sigma$-model coupled to the Einstein equations with cosmological constant $\Lambda\geq 0$ in spherical symmetry. These solutions are characterized by the presence of a regular static region which includes a center of symmetry. They are parameterized by a dimensionless ``coupling constant'' $\beta$, the sign of the cosmological constant, and an integer ``excitation number'' $n$. The phenomenology we find is compared to the corresponding solutions found for the Einstein-Yang-Mills (EYM) equations with positive $\Lambda$ (EYM$\Lambda$). If we choose $\Lambda$ positive and fix $n$, we find a family of static spacetimes with a Killing horizon for $0 \leq \beta < \beta_{max}$. As a limiting solution for $\beta = \beta_{max}$ we find a {\em globally} static spacetime with $\Lambda=0$, the lowest excitation being the Einstein static universe. To interpret the physical significance of the Killing horizon in the cosmological context, we apply the concept of a trapping horizon as formulated by Hayward. For small values of $\beta$ an asymptotically de Sitter dynamic region contains the static region within a Killing horizon of cosmological type. For strong coupling the static region contains an ``eternal cosmological black hole''.Comment: 20 pages, 6 figures, Revte

Carrying out an optimal experiment

Diffraction data collection parameters leading to optimal data quality are discussed in the context of different applications of these data

6-Hy­droxy-2,5,7,8-tetra­methyl-3,4-dihydro-2H-1-benzopyran-2-carbonitrile, from synchrotron data

The crystal structure of the title compound, C14H17NO2, solved and refined against synchrotron diffraction data, contains one formula unit in an asymmetric unit. In the crystal, mol­ecules form right-handed helices located at the 21 screw axis parallel to the a-axis direction, generated by O—H⋯N hydrogen bonding between the hy­droxy group and carbonitrile group of an adjacent mol­ecule

rac-6-Hy­droxy-2,5,7,8-tetra­methyl­chroman-2-carboxamide from synchrotron data

The crystal structure of the title water-soluble analogue of vitamin E, trolox amide, C14H19NO3, solved and refined against synchrotron diffraction data, contains two mol­ecules in the asymmetric unit. In both molecules, the heterocyclic ring is in a half-chair conformation. The crystal packing features a herring-bone pattern generated by N—H⋯O hydrogen bonds between the hy­droxy and amide groups. O—H⋯O hydrogen bonds also occur