Showing papers by "George M. Sheldrick published in 2011"

ShelXle: a Qt graphical user interface for SHELXL

Abstract: ShelXle is a graphical user interface for SHELXL [Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122], currently the most widely used program for small-molecule structure refinement. It combines an editor with syntax highlighting for the SHELXL-associated .ins (input) and .res (output) files with an interactive graphical display for visualization of a three-dimensional structure including the electron density (Fo) and difference density (Fo–Fc) maps. Special features of ShelXle include intuitive atom (re-)naming, a strongly coupled editor, structure visualization in various mono and stereo modes, and a novel way of displaying disorder extending over special positions. ShelXle is completely compatible with all features of SHELXL and is written entirely in C++ using the Qt4 and FFTW libraries. It is available at no cost for Windows, Linux and Mac-OS X and as source code.

ANODE: anomalous and heavy-atom density calculation

Abstract: The new program ANODE estimates anomalous or heavy-atom density by reversing the usual procedure for experimental phase determination by methods such as single- and multiple-wavelength anomalous diffraction and single isomorphous replacement anomalous scattering. Instead of adding a phase shift to the heavy-atom phases to obtain a starting value for the native protein phase, this phase shift is subtracted from the native phase to obtain the heavy-atom substructure phase. The required native phase is calculated from the information in a Protein Data Bank file of the structure. The resulting density enables even very weak anomalous scatterers such as sulfur to be located. Potential applications include the identification of unknown atoms and the validation of molecular replacement solutions.

Geometric properties of nucleic acids with potential for autobuilding

Abstract: Medium- to high-resolution X-ray structures of DNA and RNA molecules were investigated to find geometric properties useful for automated model building in crystallographic electron-density maps. We describe a simple method, starting from a list of electron-density `blobs', for identifying backbone phosphates and nucleic acid bases based on properties of the local electron-density distribution. This knowledge should be useful for the automated building of nucleic acid models into electron-density maps. We show that the distances and angles involving C1′ and the P atoms, using the pseudo-torsion angles \eta' and \theta\,' that describe the …P—C1′—P—C1′… chain, provide a promising basis for building the nucleic acid polymer. These quantities show reasonably narrow distributions with asymmetry that should allow the direction of the phosphate backbone to be established.

Structure of a highly NADP+-specific isocitrate dehydrogenase.

Abstract: Isocitrate dehydrogenase catalyzes the first oxidative and decarboxylation steps in the citric acid cycle. It also lies at a crucial bifurcation point between CO2-generating steps in the cycle and carbon-conserving steps in the glyoxylate bypass. Hence, the enzyme is a focus of regulation. The bacterial enzyme is typically dependent on the coenzyme nicotinamide adenine dinucleotide phosphate. The monomeric enzyme from Corynebacterium glutamicum is highly specific towards this coenzyme and the substrate isocitrate while retaining a high overall efficiency. Here, a 1.9 A resolution crystal structure of the enzyme in complex with its coenzyme and the cofactor Mg2+ is reported. Coenzyme specificity is mediated by interactions with the negatively charged 2′-­phosphate group, which is surrounded by the side chains of two arginines, one histidine and, via a water, one lysine residue, forming ion pairs and hydrogen bonds. Comparison with a previous apoenzyme structure indicates that the binding site is essentially pre­configured for coenzyme binding. In a second enzyme molecule in the asymmetric unit negatively charged aspartate and glutamate residues from a symmetry-related enzyme molecule interact with the positively charged arginines, abolishing coenzyme binding. The holoenzyme from C. glutamicum displays a 36° interdomain hinge-opening movement relative to the only previous holoenzyme structure of the monomeric enzyme: that from Azotobacter vinelandii. As a result, the active site is not blocked by the bound coenzyme as in the closed conformation of the latter, but is accessible to the substrate isocitrate. However, the substrate-binding site is disrupted in the open conformation. Hinge points could be pinpointed for the two molecules in the same crystal, which show a 13° hinge-bending movement relative to each other. One of the two pairs of hinge residues is intimately flanked on both sides by the isocitrate-binding site. This suggests that binding of a relatively small substrate (or its competitive inhibitors) in tight proximity to a hinge point could lead to large conformational changes leading to a closed, presumably catalytically active (or inactive), conformation. It is possible that the small-molecule concerted inhibitors glyoxylate and oxaloacetate similarly bind close to the hinge, leading to an inactive conformation of the enzyme.