SEQUENCE SLIDER: expanding polyalanine fragments for phasing with multiple side-chain hypotheses.

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.

Statistical tests against systematic errors in data sets based on the equality of residual means and variances from control samples: theory and applications.

Statistical tests are applied for the detection of systematic errors in data sets from least-squares refinements or other residual-based reconstruction processes. Samples of the residuals of the data are tested against the hypothesis that they belong to the same distribution. For this it is necessary that they show the same mean values and variances within the limits given by statistical fluctuations.

More about systematic errors in charge-density studies.

In order to detect and graphically visualize the absence or presence of systematic errors in fit data, conditional probabilities are employed to analyze the statistical independence or dependence of fit residuals. This concept is completely general and applicable to all scientific fields in which model parameters are fitted to experimental data. The applications presented in this work refer to published charge-density data.

Structure and cell wall cleavage by modular lytic transglycosylase MltC of Escherichia coli.

The lytic transglycosylases are essential bacterial enzymes that catalyze the nonhydrolytic cleavage of the glycan strands of the bacterial cell wall. We describe here the structural and catalytic properties of MltC, one of the seven lytic transglycosylases found in the genome of the Gram-negative bacterium Escherichia coli. The 2.

Structure solution with ARCIMBOLDO using fragments derived from distant homology models.

Molecular replacement, one of the general methods used to solve the crystallographic phase problem, relies on the availability of suitable models for placement in the unit cell of the unknown structure in order to provide initial phases. ARCIMBOLDO, originally conceived for ab initio phasing, operates at the limit of this approach, using small, very accurate fragments such as polyalanine α-helices. A distant homolog may contain accurate building blocks, but it may not be evident which sub-structure is the most suitable purely from the degree of conservation.

Structure solution of DNA-binding proteins and complexes with ARCIMBOLDO libraries.

Protein-DNA interactions play a major role in all aspects of genetic activity within an organism, such as transcription, packaging, rearrangement, replication and repair. The molecular detail of protein-DNA interactions can be best visualized through crystallography, and structures emphasizing insight into the principles of binding and base-sequence recognition are essential to understanding the subtleties of the underlying mechanisms. An increasing number of high-quality DNA-binding protein structure determinations have been witnessed despite the fact that the crystallographic particularities of nucleic acids tend to pose specific challenges to methods primarily developed for proteins.

Fundamental relation between molecular geometry and real-space topology. Combined AIM, ELI-D, and ASF analysis of hapticities and intramolecular hydrogen-hydrogen bonds in zincocene-related compounds.

Despite numerous advanced and widely distributed bonding theories such as MO, VB, NBO, AIM, and ELF/ELI-D, complex modes of bonding such as M-Cp*((R)) interactions (hapticities) in asymmetrical metallocenes or weak intramolecular interactions (e.g., hydrogen-hydrogen (H···H) bonds) still remain a challenge for these theories in terms of defining whether or not an atom-atom interaction line (a "chemical bond") should be drawn.

About systematic errors in charge-density studies.

The formerly introduced theoretical R values [Henn & Schönleber (2013). Acta Cryst. A69, 549-558] are used to develop a relative indicator of systematic errors in model refinements, R(meta), and applied to published charge-density data.

Exploiting tertiary structure through local folds for crystallographic phasing.

We describe an algorithm for phasing protein crystal X-ray diffraction data that identifies, retrieves, refines and exploits general tertiary structural information from small fragments available in the Protein Data Bank. The algorithm successfully phased, through unspecific molecular replacement combined with density modification, all-helical, mixed alpha-beta, and all-beta protein structures. The method is available as a software implementation: Borges.

The structure of the oligomerization domain of Lsr2 from Mycobacterium tuberculosis reveals a mechanism for chromosome organization and protection.

Lsr2 is a small DNA-binding protein present in mycobacteria and related actinobacteria that regulates gene expression and influences the organization of bacterial chromatin. Lsr2 is a dimer that binds to AT-rich regions of chromosomal DNA and physically protects DNA from damage by reactive oxygen intermediates (ROI). A recent structure of the C-terminal DNA-binding domain of Lsr2 provides a rationale for its interaction with the minor groove of DNA, its preference for AT-rich tracts, and its similarity to other bacterial nucleoid-associated DNA-binding domains.

Practical structure solution with ARCIMBOLDO.

Since its release in September 2009, the structure-solution program ARCIMBOLDO, based on the combination of locating small model fragments such as polyalanine α-helices with density modification with the program SHELXE in a multisolution frame, has evolved to incorporate other sources of stereochemical or experimental information. Fragments that are more sophisticated than the ubiquitous main-chain α-helix can be proposed by modelling side chains onto the main chain or extracted from low-homology models, as locally their structure may be similar enough to the unknown one even if the conventional molecular-replacement approach has been unsuccessful. In such cases, the program may test a set of alternative models in parallel against a specified figure of merit and proceed with the selected one(s).

High-resolution crystal structure of MltE, an outer membrane-anchored endolytic peptidoglycan lytic transglycosylase from Escherichia coli.

The crystal structure of the first endolytic peptidoglycan lytic transglycosylase MltE from Escherichia coli is reported here. The degradative activity of this enzyme initiates the process of cell wall recycling, which is an integral event in the existence of bacteria. The structure sheds light on how MltE recognizes its substrate, the cell wall peptidoglycan.

Is there a fundamental upper limit for the significance I/σ(I) of observations from X-ray and neutron diffraction experiments?

The answer is yes. A fundamental limit exists, which is not strongly applicable to individual reflections but to a sufficiently large set of reflections such as any set for structure determination. The limit originates from Poisson statistics which gives a minimum (average) error.

Synthesis, structure, and theoretical investigation of amidinato supported 1,4-disilabenzene.

Reaction of LSi-SiL (1) (L = PhC(NtBu)(2)) with diphenyl alkyne gave the first example of a room temperature stable 1,4-disilabenzene. The compound was characterized by means of single crystal X-ray diffraction studies. NICS (nucleus independent chemical shift) calculations showed that the compound has some aromatic character.

The first asymmetric organolithium tetramers with simple ether donor bases.

The donor-free trimethylsilylmethyllithium [LiCH(2)SiMe(3)](6) hexameric aggregate is for the first time broken up by simple ether donors such as diethyl ether (Et(2)O) and tert-butylmethyl ether ((t)BuOMe) to give the unprecedented asymmetric tetramers while the chelating dimethoxyethane (DME) gives the expected dimer.

On the effect of neglecting anharmonic nuclear motion in charge density studies.

The effect of neglecting anharmonic nuclear motion when it is definitely present is studied. To ensure the presence of anharmonic nuclear motion a model was used that was previously refined against experimental data including anharmonic nuclear motion, and these calculated structure factors were used as observed data for a multipole refinement. It was then studied how the neglect of anharmonic nuclear motion and noise in the data affects the usual crystallographic quality measure R, the density parameters and the residual density distribution.

Lewis-base-stabilized dichlorosilylene: a two-electron sigma-donor ligand.

The first structurally described cobalt(I) Lewis-base-stabilized silylene complex [Co(CO)(3){SiCl(2)(IPr)}(2)](+)[CoCl(3)(THF)](-) [1; IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene] was prepared by applying the two-electron sigma-donor ligand SiCl(2)(IPr) through coordination with Co(2)(CO)(8). The bonding situation between ligand SiCl(2)(IPr) and the cobalt(I) metal center in [Co(CO)(3){SiCl(2)(IPr)}(2)](+) of 1 was investigated by (1)H NMR and IR spectroscopy, single-crystal X-ray structural analysis, and density functional theoretical calculations.

Experimental charge density studies of disordered N-phenylpyrrole and N-(4-fluorophenyl)pyrrole.

The static electron densities of the title compounds were extracted from high-resolution X-ray diffraction data using the nucleus-centered finite multipole expansion technique. The interpretation of the data collected for the N-phenylpyrrole crystal revealed a static disorder that could be successfully resolved within the aspherical-atom formalism. The local and integrated topological properties of the density obtained via a constrained multipole refinement are in statistical agreement with those calculated at the B3LYP/cc-pVTZ level of theory for the isolated molecule and for those derived from the experimental density of the para-fluorinated derivative N-(4-fluorophenyl)pyrrole.

Synthesis and characterization of alkynyl complexes of groups 1 and 2.

The synthesis of N-heterocyclic carbene adducts of alkynyl lithium and magnesium is achieved, and different degrees of association are observed. Reaction of strontium amide nacnacSrN(SiMe(3))(2)(thf) (nacnac = CH(CMe2,6-iPr(2)C(6)H(3)N)(2)) with PhC[triple bond]CH in THF yields the dimeric alkynyl complex [nacnacSr(thf)(mu-C[triple bond]CPh)](2) which shows an interesting coordination geometry around the metal center. The compound retains the THF molecules, unlike its lighter congener, even in hydrocarbon solvents.

6-Benzyl-3,4-dimeth-oxy-10-methyl-pyrido[2',1':2,3]imidazo[4,5-c]isoquinolin-5(6H)-one.

Pyrido[2',1':2,3]imidazo[4,5-c]isoquinolin-5(6H)-ones such as the title compound, C(24)H(21)N(3)O(3), can be obtained in a few minutes in a microwave-assisted three-component reaction from 2-amino-pyridines, isocyanides and 2-carboxy-benz-aldehydes. In the title compound, the pyrido[2',1':2,3]imidazo[4,5-c]isoquinolin-5(6H)-one ring system is almost planar (mean deviation 0.068 Å).

Foundations of residual-density analysis.

New and concise descriptors of the residual density are presented, namely the gross residual electrons, the net residual electrons and the fractal dimension distribution. These descriptors indicate how much residual density is present and in what way it is distributed, i.e.