A5028801665- Enzyme Structure and Function
- Protein Structure and Dynamics
- Silicon Nanostructures and Photoluminescence
- Enzyme Production and Characterization
- Bacterial Genetics and Biotechnology
- Particle physics theoretical and experimental studies
- High-Energy Particle Collisions Research
- Semiconductor materials and devices
- Nanowire Synthesis and Applications
- Silicon Carbide Semiconductor Technologies
- Distributed and Parallel Computing Systems
- Glycosylation and Glycoproteins Research
- Graphene research and applications
- RNA and protein synthesis mechanisms
- Semiconductor materials and interfaces
- Anodic Oxide Films and Nanostructures
- Endoplasmic Reticulum Stress and Disease
- Neurotransmitter Receptor Influence on Behavior
- Amino Acid Enzymes and Metabolism
- Redox biology and oxidative stress
- Scientific Computing and Data Management
- Biochemical and Molecular Research
- Advanced ceramic materials synthesis
- Bacteriophages and microbial interactions
- Particle Detector Development and Performance
Research Complex at Harwell
2013-2025
Rutherford Appleton Laboratory
2015-2025
N. I. Lobachevsky State University of Nizhny Novgorod
2024
Institute of Applied Physics
2024
Research Institute "Quantum"
2024
Didcot Community Hospital
2023
Science and Technology Facilities Council
2015-2022
European Bioinformatics Institute
2019
Ioffe Institute
2010-2019
GSI Helmholtz Centre for Heavy Ion Research
2010-2019
This paper describes various components of the macromolecular crystallographic refinement program REFMAC5, which is distributed as part CCP4 suite. REFMAC5 utilizes different likelihood functions depending on diffraction data employed (amplitudes or intensities), presence twinning and availability SAD/SIRAS experimental data. To ensure chemical structural integrity refined model, offers several classes restraints choices model parameterization. Reliable models at resolutions least low 4 Å...
One of the most important aspects macromolecular structure refinement is use prior chemical knowledge. Bond lengths, bond angles and other properties are used in restrained as subsidiary conditions. This contribution describes organization some flexible human/machine-readable dictionary knowledge by maximum-likelihood macromolecular-refinement program REFMAC5. The stores information about monomers which represent constitutive building blocks biological macromolecules (amino acids, nucleic...
The CCP4 (Collaborative Computational Project, Number 4) software suite for macromolecular structure determination by X-ray crystallography groups brings together many programs and libraries that, means of well established conventions, interoperate effectively without adhering to strict design guidelines. Because this inherent flexibility, users are often presented with diverse, even divergent, choices solving every type problem. Recently, introduced CCP4i2, a modern graphical interface...
Biological macromolecules are polymers and therefore the restraints for macromolecular refinement can be subdivided into two sets: that applied to atoms all belong same monomer associated with covalent bonds between monomers. The CCP4 template-restraint library contains three types of data entries defining template restraints: descriptions monomers their modifications, both used intramonomer restraints, links intermonomer restraints. provides generic modifications protein, DNA RNA chains,...
The Collaborative Computational Project No. 4 (CCP4) is a UK-led international collective with mission to develop, test, distribute and promote software for macromolecular crystallography. CCP suite multiplatform collection of programs brought together by familiar execution routines, set common libraries graphical interfaces. has experienced several considerable changes since its last reference article, involving new infrastructure, original This which intended as general literature citation...
Nowadays, progress in the determination of three-dimensional macromolecular structures from diffraction images is achieved partly at cost increasing data volumes. This due to deployment modern high-speed, high-resolution detectors, increased complexity and variety crystallographic software, use extensive databases high-performance computing. limits what can be accomplished with personal, offline, computing equipment terms both productivity maintainability. There also an issue long-term...
The success of molecular replacement is critically dependent on the quality search model. Several model-preparation procedures are integrated in molecular-replacement program MOLREP. These include model modification basis amino-acid sequence alignment and correction based analysis solvent-accessibility atoms. packing function used MOLREP for translational explained context preparation. In difficult cases, bioinformatics-based modifications not sufficient successful replacement. An approach...
It is not uncommon for protein crystals to crystallize with more than a single molecule per asymmetric unit. When present in the unit, various pathological situations such as twinning, modulated and pseudo translational or rotational symmetry can arise. The presence of pseudosymmetry lead uncertainties about correct space group, especially twinning. background certain common pathologies presented new notation groups unusual settings introduced. main concepts are illustrated several examples...
The presence of pseudo-symmetry in a macromolecular crystal and its interplay with twinning may lead to an incorrect space-group (SG) assignment. Moreover, if the is very close exact crystallographic symmetry, structure can be solved partially refined wrong SG. Typically, such incorrectly determined structures all or some operations are, effect, taken for symmetry vice versa . A mistake only becomes apparent when R free ceases decrease below 0.39 further model rebuilding refinement cannot...
Microsomal triglyceride transfer protein (MTP) plays an essential role in lipid metabolism, especially the biogenesis of very low-density lipoproteins and chylomicrons via neutral lipids assembly apoB-containing lipoproteins. Our understanding molecular mechanisms MTP has been hindered by a lack structural information this heterodimeric complex comprising MTPα subunit disulfide isomerase (PDI) β-subunit. The structure presented here gives important insights into potential action molecule,...
Modern crystallographic computing is characterized by the growing role of automated structure-solution pipelines, which represent complex expert systems utilizing a number program components, decision makers and databases. They also require considerable computational resources regular database maintenance, increasingly more difficult to provide at level individual desktop-based CCP 4 setups. On other hand, there significant growth in data processed field, brings up issue centralized...
ARCIMBOLDO solves the phase problem by combining location of small model fragments using Phaser with density modification and autotracing SHELXE. Mainly helical structures constitute favourable cases, which can be solved polyalanine as search models. Nevertheless, solution coiled-coil is often complicated their anisotropic diffraction apparent translational noncrystallographic symmetry. Long, straight helices have internal symmetry alignment in preferential directions gives rise to...
The human C-type lectin-like molecule CLEC5A is a critical macrophage receptor for dengue virus. binding of virus to triggers signaling through the associated adapter DAP12, stimulating proinflammatory cytokine release. We have crystallized an informative ensemble structural conformers at 1.9-Å resolution and demonstrate how on-off extension β-sheet acts as binary switch regulating flexibility molecule. This information together with molecular dynamics simulations suggests mechanism whereby...
Hemolysin co-regulated protein 1 (Hcp1) is a component of the cluster Type VI secretion system (T6SS1) that plays key role during intracellular lifecycle Burkholderia pseudomallei . Hcp1 recognized as promising target antigen for developing melioidosis diagnostics and vaccines. While gene encoding retained across B strains, variants hcp1 have recently been identified. This study aimed to examine prevalence in clinical isolates , assess antigenicity variants, ability strains expressing these...
Endo-galactosaminidases are an underexplored family of enzymes involved in the degradation galactosaminogalactan (GAG) and other galactosamine-containing cationic exopolysaccharides produced by fungi bacteria. These part cell wall extracellular matrix microbial communities. Currently, these galactosaminidases found three distinct CAZy families: GH114, GH135 GH166. Despite widespread occurrence nearly all bacterial fungal clades, only limited biochemical structural data available for groups....
Entries deposited in the Protein Data Bank as of February 2004 for which both model and X-ray data were available analysed to identify cases twinning using such simple statistics R factor between potential twin-related reflections. Careful consideration all identified twins showed that many was ignored during structure solution refinement. Manual analysis models often occurs association with rotational pseudosymmetry parallel operator. The coexistence these two phenomena complicates...
Two-component systems (TCS) represent major signal-transduction pathways for adaptation to environmental conditions, and regulate many aspects of bacterial physiology. In the whooping cough agent Bordetella pertussis, TCS BvgAS controls virulence regulon, is therefore critical pathogenicity. BvgS a prototypical sensor-kinase with tandem periplasmic Venus flytrap (VFT) domains. VFT are bi-lobed domains that typically close around specific ligands using clamshell motions. We report X-ray...
Mixed Lineage Leukemia 5 (MLL5) plays a key role in hematopoiesis, spermatogenesis and cell cycle progression. Chromatin binding is ensured by its plant homeodomain (PHD) through direct interaction with the N-terminus of histone H3 (H3). In addition, MLL5 contains Su(var)3-9, Enhancer zeste, Trithorax (SET) domain, protein module that usually displays lysine methyltransferase activity. We report here crystal structure unliganded SET domain human at 2.1 Å resolution. Although it shows most...