Papers by Bohdan Schneider
Acta Crystallographica, Aug 14, 2021
Proteins and nucleic acids evolved in the aqueous environment, and water is therefore deeply inte... more Proteins and nucleic acids evolved in the aqueous environment, and water is therefore deeply interrelated with both biomolecular structure and function. The first layer of water molecules around the biomolecular surface-the hydration shell-has properties different from the bulk water [1]. The dynamics of these water molecules is significantly reduced, and the shell mostly consists of ordered (localized) water molecules. However, the first shell water molecules do not have an ice-like structural properties. These ordered water molecules play significant role in recognition and binding of ligands. In our work, we utilize crystallographic data to compile the average hydration patterns around biomolecules. Firstly, we investigated hydration of DNA building blocks [2, 3], and later hydration of amino acids in proteins as a function of their rotameric state and the secondary structure [4, 5]. Recently, we analyzed hydration of DNA dinucleotides as a function of their conformation and sequence [6]. Here, we present an overview of these results as well as the methodology we used to obtain the data and the potential application of the results.
Annual meeting of the Czech and Slovak Association 2012 takes place in Klatovy, the most west poi... more Annual meeting of the Czech and Slovak Association 2012 takes place in Klatovy, the most west point in history of these meetings. It is devoted to computational methods in structure analysis and largely to courses on software-for structure determination and refinement FOX and Jana, to real structure evaluation MSTRUCT and to semiautomatic search of ligands in protein structures. Three reviews included at the beginning of this issue are followed by the abstracts of 14 lecturers and 23 short contributions. Nearly 70 participants were registered at the time of the journal printing. Electronic version of the journal can be found at
The FEBS Journal, 2021
We hereby describe the process of design and selection of non-antibody protein binders mimicking ... more We hereby describe the process of design and selection of non-antibody protein binders mimicking cytokine signaling. We chose to mimic signaling of IFN-λ1, type 3 interferon (also known as IL-29) for its novelty and the importance of its biological functions. All four known interferons λ signal through binding to the extracellular domains of IL-28 receptor 1 (IL-28R1) and IL-10 receptor 2 (IL-10R2). Our binders were therefore trained to bind both receptors simultaneously. The bifunctional binder molecules were developed by yeast display, a method of directed evolution. The signaling capacity of the bivalent binders was tested by measuring phosphorylation of the JAK/STAT signaling pathway and production of mRNA of six selected genes naturally induced by IFN- λ1 in human cell lines. The newly developed bivalent binders offer opportunities to study cytokine-related biological functions and modulation of the cell behavior by receptor activation on the cell surfaces alternative to the use of natural IFN- λ.
Acta Crystallographica Section A Foundations and Advances, 2017
We will present an easy-to-use and automated tool providing comprehensive description of DNA stru... more We will present an easy-to-use and automated tool providing comprehensive description of DNA structures and demonstrate its usefulness for understanding of protein-DNA interactions. Our description of DNA structure is based on definitions of distinct dinucleotide conformers and their assembly into-to the best of our knowledge-the first structural alphabet of nucleic acids. The alphabet is called CANA (Conformational Alphabet of Nucleic Acids) and consists of thirteen letters for various DNA conformer classes. CANA describes the DNA structural variability way beyond the traditionally used classification schema into A-form, B-form, and Z-form, but at the same time simplifies DNA structural description by transforming complex 3D structural information into the symbolic CANA alphabet. The CANA letters are assigned by an automated procedure available at the web sites dnatco.org [1] and dolbico.org to any PDB formatted structure. The assignment protocol translates 3D DNA structures into textual and/or graphical symbolic language of the CANA letters and streamlines thus human understanding of the complicated molecular structure. By using the CANA alphabet, we describe the structural variability of prototypical DNA structures such as Dickerson-Drew dodecamer and guanine quadruplexes, and critically discuss structural models based on the fiber diffraction. We address the challenge of understanding the specificity of protein-DNA interactions by analyzing CANA words typical for different types of protein-DNA complexes such as various types of transcription factors or histone core particle and compare the patterns of the CANA words in protein-bound and solvent-exposed DNA in these complexes. As an example of the results, Fourier transform of the occurrence of CANA letters of DNA in crystal structures of histone core reveals that one of the letters occurs every 10th step, i. e. every helical turn. Analysis of DNA structure based on the structural alphabet contributed thus to the understanding of the origin of DNA positioning around the histone core proteins.
Journal of Applied Crystallography, 2020
Electron crystallography of sub-micrometre-sized 3D protein crystals has emerged recently as a va... more Electron crystallography of sub-micrometre-sized 3D protein crystals has emerged recently as a valuable field of structural biology.In mesocrystallization methods, utilizing lipidic mesophases, particularly lipidic cubic phases (LCPs), can produce high-quality 3D crystals of membrane proteins (MPs). A major step towards realizing 3D electron crystallography of MP crystals, grownin meso, is to demonstrate electron diffraction from such crystals. The first task is to remove the viscous and sticky lipidic matrix that surrounds the crystals without damaging the crystals. Additionally, the crystals have to be thin enough to let electrons traverse them without significant multiple scattering. In the present work, the concept that focused ion beam milling at cryogenic temperatures (cryo-FIB milling) can be used to remove excess host lipidic mesophase matrix is experimentally verified, and then the crystals are thinned to a thickness suitable for electron diffraction. In this study, bacteri...
Acta Crystallographica Section A Foundations and Advances, 2018
The FEBS Journal, 2019
Interleukin 24 (IL‐24) is a cytokine with the potential to be an effective treatment for autoimmu... more Interleukin 24 (IL‐24) is a cytokine with the potential to be an effective treatment for autoimmune diseases and cancer. However, its instability and difficulties in its production have hampered detailed biological and biophysical studies. We approached the challenges of IL‐24 production by using the PROSS algorithm to design more stable variants of IL‐24. We used homology models built from the sequences and known structures of IL‐20 and IL‐19 and predicted and produced several extensively mutated IL‐24 variants that were highly stable and produced in large yields; one of them was crystallized (IL‐24B, PDB ID 6GG1; 3D Interactive at http://proteopedia.org/w/Journal: FEBS_Journal:1). The mutated variants, however, lost most of their binding capacity to the extracellular parts of cognate receptors. While the affinity to the receptor 2 (IL‐20R2) was preserved, the variants lost affinity to IL‐20R1 and IL‐22R1 (shared receptors 1). Back engineering of the variants revealed that reintrod...
Acta Crystallographica Section A Foundations of Crystallography, 1996
CRYSTALLOGRAPHY OF BIOLOGICAL MACROMOLECULES basis of the interactions observed in the enzyme-inh... more CRYSTALLOGRAPHY OF BIOLOGICAL MACROMOLECULES basis of the interactions observed in the enzyme-inhibitor complex, implicate the side chain of Leu-272 in active expulsion of uracil from DNA by penetrating the DNA helix from the major groove, with the uracil "nipping out" via the DNA minor groove. Recent results conoborate this hypothesis and suggest a mechanism for UDG recognition of promutagenic GU mismatch base pairs within the context of double-stranded DNA.
Journal of Molecular Structure: THEOCHEM, 1986
The title calculations were performed with the aim of providing data for the critical examination... more The title calculations were performed with the aim of providing data for the critical examination of the utility of the basis set superposition error (BSSE) correction. The main results obtained are as follows. The SCF interaction energies corrected for the BSSE and evaluated with the basis sets of split-valence and DZ origin are similar. With the stabilization energy, both the basis set superposition error and the intersystem correlation energy are important. MP2 stabilization energies are only slightly dependent on basis set for basis sets of DZ + P or better quality. The basis set superposition error at both the SCF and MP2 levels remains almost unchanged when passing from the 6-31G* to the 6-311G(2d, 2p) basis set. At the SCF level sufficiently accurate geometries were obtained with the standard 6-31G* basis set. Optimization at the MP2 level with this and larger basis sets brings about oniy smaii changes with respect to optimum SCF geometries.
Acta Crystallographica Section C-Crystal Structure Communications, 1990
... C(12) 50339 (8) 2002 (2) 9501 (2) 455 (7) C(13) 52727 (8) 1067 (2) 8849 (2) 458 (7) C(14) 575... more ... C(12) 50339 (8) 2002 (2) 9501 (2) 455 (7) C(13) 52727 (8) 1067 (2) 8849 (2) 458 (7) C(14) 57549 (7) 1166 (2) 8764 (I) 424 (6) O(15) 60330 (5) 305 (2) 8172 (1) 561 (5) C(l 6) 58223 (10) - 855 (2) 7652 (2) 542 (8) C(17) 60080 (7) 2203 (2) 9328 (2) 450 (7) O(18) 64827 (5) 2232 ...
PLoS Computational Biology, 2006
Collection of Czechoslovak Chemical Communications, 1990
Three-dimensional crystal structures of a diphenyl sulfide skeleton from various compounds were c... more Three-dimensional crystal structures of a diphenyl sulfide skeleton from various compounds were confronted with computed conformational map. Diphenyl sulfide fragments, 31 in total, were retrieved from the Cambridge Structural Database and four fragments were taken from our measurements. Due to the symmetry of the fragment, the number of analyzed fragments rose to 140. The main features of geometrical behaviour of the fragment can be summarized as follows: If an endocyclic torsion angle of a phenyl ring deviates from 0 °C, the adjacent torsion angle is deformed in opposite direction by the same value keeping thus the phenyl ring planar. Repulsion of phenyl rings enlarges a C-S-C bonding angle in all fragments and bends aside the phenyl ring from a symmetrical attachment which has torsion around a S-C bond near 0°. Torsion angles around the S-C bonds correlate with each other keeping approximately perpendicular orientation of the phenyl rings. The correspondence between experimental ...
Collection of Czechoslovak Chemical Communications, 1990
The crystal and molecular structure of the title compound, C19H21NO5S, M = 375.44, was solved by ... more The crystal and molecular structure of the title compound, C19H21NO5S, M = 375.44, was solved by X-ray structure analysis using diffractometer intensity measurement with CuKα radiation. The space group is P1, with lattice parameters a = 555.7(3), b = 1 697.0(8), c = 1 035.4(4) pm, α = 106.77(4)°, β = 98.19(4)°, γ = 90.64(4)°, V = 923.9(8) . 106 pm3, Z = 2, ρcalc = 1.349 g/cm3, ρm = 1.32 g/cm3. Anisotropic refinement of all nonhydrogen and isotropic refinement of eight hydrogen atoms converged to R = 0.056 and wR = 0.114 for 2 481 observed reflections. Hydrogen bonds O18-H181···O25 and N9-H91···O24i join neighbouring diphenyl sulphide and maleate molecules to linear chains. The parallel chains interact through van der Waals contacts only. Molecules of maleic acid are nearly planar keeping π-electron delocalization. An angle between phenyl rings of the diphenyl sulphide molecule is 80.9(1)° and torsion angles around S-C bonds are 23.2(3)° and 73.6(3)°.
![Research paper thumbnail of 4H-Benzo[4,5]cyclohepta[1,2-b]thiophenes and 9,10-dihydro derivatives - Sulfonium analogues of pizotifen and ketotifen; Chirality of ketotifen; Synthesis of the 2-bromo derivative of ketotifen](https://attachments.academia-assets.com/106918012/thumbnails/1.jpg)
Collection of Czechoslovak Chemical Communications, 1989
Reaction of ketone IX with 4-tetrahydrothiopyranylmagnesium bromide and the following dehydration... more Reaction of ketone IX with 4-tetrahydrothiopyranylmagnesium bromide and the following dehydration with thionyl chloride afforded the sulfide III which was transformed to the methiodide II (sulfonium analogue of pizotifen). Similar sequence starting from the ketone XXIV and concluded by dehydration of the alcohol XX, cleavage of the enol ether, and by treatment with methyl iodide resulted in the formation of the sulfonium analogue of ketotifen (V). Three modified routes leading to ketotifen (IV) are being described. The chirality of ketotifen was proven by 1H NMR spectroscopy with the help of the optically active NMR shift reagent. The resolution of racemic ketotifen (IV) was achieved by crystallization of salts with optically active O,O'-diacyltartaric acids and homogeneous enantiomers were obtained. The X-ray crystallographic analysis of (+)-IV (-)-O,O'-di(p-toluoyl)-(R)-tartarate led to the three-dimensional structure of the molecule of (+)-ketotifen which enabled to deter...
Chemical Physics Letters, 1987
The energy of formation of the T-shaped (HZ)* dimer is calculated using different basis sets and ... more The energy of formation of the T-shaped (HZ)* dimer is calculated using different basis sets and Mdller-Plesset perturbation theory up to fourth order. The roles of the second-, third-and fourth-order contributions as well as that of the different excitations at the fourth-order level were investigated. The results suggest that a correction for basis set superposition error should be included at both the SCF and post-SCF levels.
Acta Crystallographica Section D Biological Crystallography, 2008
Acta Crystallographica Section A Foundations of Crystallography, 2002
Profilin is a regulatory component of the actin cytoskeleton in all eucaryotic cells, which binds... more Profilin is a regulatory component of the actin cytoskeleton in all eucaryotic cells, which binds actin, proline-rich peptides and phosphatidylinositol 4,5biphosphate (PIP2). The crystal structures of profilin-II from Acanthamoeba castellani and yeast profilin from Sacharomyces Cerevisiae have been determined by molecular replacement and refined at 2.3 Å resolution to R=22.9%, Rfree=28.7% and R=21.1%,Rfree=23.0%, respectively, with good geometry. Both proteins crystallized in the cubic space group P4332. The structural comparisons of these two profilins with other bacterial, plant and mammalian profilins will be presented. One glycerol molecule from the cryoprotectant solvent was found to be bound in the solvent-filled pocket located near the poly-L-proline (PLP) binding site in yeast profilin. The glycerol alcohol groups form hydrogen bonds to aromatic residues involved in PLP binding in yeast profilin. These residues are conserved in all profilins and could possibly accomodate negatively charged functionalities of the PIP2 head group.
Acta Crystallographica, Dec 1, 2017
We will present an easy-to-use and automated tool providing comprehensive description of DNA stru... more We will present an easy-to-use and automated tool providing comprehensive description of DNA structures and demonstrate its usefulness for understanding of protein-DNA interactions. Our description of DNA structure is based on definitions of distinct dinucleotide conformers and their assembly into-to the best of our knowledge-the first structural alphabet of nucleic acids. The alphabet is called CANA (Conformational Alphabet of Nucleic Acids) and consists of thirteen letters for various DNA conformer classes. CANA describes the DNA structural variability way beyond the traditionally used classification schema into A-form, B-form, and Z-form, but at the same time simplifies DNA structural description by transforming complex 3D structural information into the symbolic CANA alphabet. The CANA letters are assigned by an automated procedure available at the web sites dnatco.org [1] and dolbico.org to any PDB formatted structure. The assignment protocol translates 3D DNA structures into textual and/or graphical symbolic language of the CANA letters and streamlines thus human understanding of the complicated molecular structure. By using the CANA alphabet, we describe the structural variability of prototypical DNA structures such as Dickerson-Drew dodecamer and guanine quadruplexes, and critically discuss structural models based on the fiber diffraction. We address the challenge of understanding the specificity of protein-DNA interactions by analyzing CANA words typical for different types of protein-DNA complexes such as various types of transcription factors or histone core particle and compare the patterns of the CANA words in protein-bound and solvent-exposed DNA in these complexes. As an example of the results, Fourier transform of the occurrence of CANA letters of DNA in crystal structures of histone core reveals that one of the letters occurs every 10th step, i. e. every helical turn. Analysis of DNA structure based on the structural alphabet contributed thus to the understanding of the origin of DNA positioning around the histone core proteins.
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Papers by Bohdan Schneider