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The structural biology of today is the pharmacology, therapy, and biotechnology of tomorrow

A gateway to realm of structural data for biochemists, biophysicists, molecular biologist, and all scientists whose research benefits from accurate structure determination of biological macromolecules, assemblies, and complex molecular machineries at atomic resolution.

Open access to 10 high-end core facilities and assisted expertise in NMR, X-ray crystallography and crystallization, cryo-electron microscopy and tomography, biophysical characterization of biomolecular interaction, nanobiotechnology, proteomics and structural mass spectrometry.

A distributed infrastructure constituted by Core Facilities of CEITEC (Central European Institute of Technology), located in Brno, and BIOCEV (Biotechnology and Biomedicine Centre), located in Vestec near Prague, Central Bohemia.

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CIISB Research Results

M. Forinová, et al.: A comparative assessment of a piezoelectric biosensor based on a new antifouling nanolayer and cultivation methods: Enhancingi S. aureus detection in fresh dairy products, Curr. Res. Biotechnol., 6 (2023) 6, 10.1016/j.crbiot.2023.100166

T. Pokorny, et al.: Copper Phosphinate Complexes as Molecular Precursors for Ethanol Dehydrogenation Catalysts, Inorganic Chemistry, 62 (2023) 19871-19886, 10.1021/acs.inorgchem.3c01678

M. Nemergut, et al.: Illuminating the mechanism and allosteric behavior of NanoLuc luciferase, Nature Communications, 14 (2023) 20, 10.1038/s41467-023-43403-y

A. Kertisová, et al.: Insulin receptor Arg717 and IGF-1 receptor Arg704 play a key role in ligand binding and in receptor activation, Open Biol, 13 (2023) 14, 10.1098/rsob.230142

J. Blahut, et al.: Optimal control derived sensitivity-enhanced CA-CO mixing sequences for MAS solid-state NMR - Applications in sequential protein backbone assignments, J. Magn. Reson. Open, 16-17 (2023) 9, 10.1016/j.jmro.2023.100122

Q.L. Long, et al.: The phosphorylated trimeric SOSS1 complex and RNA polymerase II trigger liquid-liquid phase separation at double-strand breaks, Cell Reports, 42 (2023) 25, 10.1016/j.celrep.2023.113489

I. Doroshenko, et al.: Structurally diverse copper(II) phosphonates: Synthesis, structure, and magnetism, Polyhedron, 246 (2023) 11, 10.1016/j.poly.2023.116694

M. Chvojka, et al.: Tuning CH Hydrogen Bond-Based Receptors toward Picomolar Anion Affinity via the Inductive Effect of Distant Substituents, Angewandte Chemie-International Edition, (2023) 7, 10.1002/anie.202318261

More publications

CIISB Research Highlights

the best of science obtained using CIISB Core Facilities

  • Nature Communications 2023 - 4

    Nature Communications 2023 - 4

    Close-up view of FMA-binding pocket with residues creating the active site in stick representation. Key hydrogen bonds are shown as dashed yellow lines.

    Martin Marek Research Group

    Significance

    NanoLuc, a superior β-barrel fold luciferase, was engineered 10 years ago but the nature of its catalysis remains puzzling. Here experimental and computational techniques are combined, revealing that imidazopyrazinone luciferins bind to an intra-barrel catalytic site but also to an allosteric site shaped on the enzyme surface. Structurally, binding to the allosteric site prevents simultaneous binding to the catalytic site, and vice versa, through concerted conformational changes. We demonstrate that restructuration of the allosteric site can boost the luminescent reaction in the remote active site. Mechanistically, an intra-barrel arginine coordinates the imidazopyrazinone component of luciferin, which reacts with O2 via a radical charge-transfer mechanism, and then it also protonates the resulting excited amide product to form a light-emitting neutral species. Concomitantly, an aspartate, supported by two tyrosines, fine-tunes the blue color emitter to secure a high emission intensity. This information is critical to engineering the next-generation of ultrasensitive bioluminescent reporters.

    Nemergut, M., Pluskal, D., Horackova, J. et al. Illuminating the mechanism and allosteric behavior of NanoLuc luciferase.

    Nat Commun 14, 7864 (2023). https://doi.org/10.1038/s41467-023-43403-y

  • Angewandte Chemie Int. Ed. 2023

    Angewandte Chemie Int. Ed. 2023

    Ultrahigh binding affinity of bambusuril receptors toward halides is achieved and continuously increases with increasing electron-withdrawing power of groups installed on its benzyl substituents, as measured by 1H and 19F NMR spectroscopy.

    Vladimír Šindelář Research Group

    Significance

    Inspired by nature, artificial hydrogen bond-based anion receptors have been developed to achieve high anion selectivity; however, their binding affinity is usually low. The potency of these receptors is usually increased by the introduction of aryl substituents, which withdraw electrons from their binding site through the resonance effect. Here, we show that the polarization of the C(sp3)-H binding site of bambusuril receptors, and thus their potency to bind anions, can be modulated by the inductive effect. The presence of electron-withdrawing groups on benzyl substituents of bambusurils significantly increases their binding affinities to halides, resulting in the strongest iodide receptor reported to date with an association constant greater than 1013 M−1 in acetonitrile. A Hammett plot showed that while the bambusuril affinity toward halides linearly increases with the electron-withdrawing power of their substituents, their binding selectivity remains essentially unchanged.

    Tuning CH Hydrogen Bond-Based Receptors toward Picomolar Anion Affinity via the Inductive Effect of Distant Substituents, M. Chvojka, D. Madea, H. Valkenier, V. Šindelář

    Angew. Chem. Int. Ed. 2023, e202318261. https://doi.org/10.1002/anie.202318261

  • Cell Reports 2023-2

    Cell Reports 2023-2

    Double-strand breaks (DSBs) are the most severe type of DNA damage. Long et al. show that hSSB1 is modified and forms a trimeric SOSS1 complex that comes to DSBs in an R-loop-dependent manner. At DSBs, SOSS1 and RNA polymerase II form liquid-like repair compartments. Depletion of the SOSS1 impairs DNA repair.

    Monika Gullerova Research Group

    Significance

    Double-strand breaks (DSBs) are the most severe type of DNA damage. Previously, we demonstrated that RNA polymerase II (RNAPII) phosphorylated at the tyrosine 1 (Y1P) residue of its C-terminal domain (CTD) generates RNAs at DSBs. However, the regulation of transcription at DSBs remains enigmatic. Here, we show that the damage-activated tyrosine kinase c-Abl phosphorylates hSSB1, enabling its interaction with Y1P RNAPII at DSBs. Furthermore, the trimeric SOSS1 complex, consisting of hSSB1, INTS3, and c9orf80, binds to Y1P RNAPII in response to DNA damage in an R-loop-dependent manner. Specifically, hSSB1, as a part of the trimeric SOSS1 complex, exhibits a strong affinity for R-loops, even in the presence of replication protein A (RPA). Our in vitro and in vivo data reveal that the SOSS1 complex and RNAPII form dynamic liquid- like repair compartments at DSBs. Depletion of the SOSS1 complex impairs DNA repair, underscoring its biological role in the R-loop-dependent DNA damage response.

    Long, QL; Sebesta, M; Sedova, K; Haluza, V; Alagia, A; Liu, ZC; Stefl, R; Gullerova, M: The phosphorylated trimeric SOSS1 complex and RNA polymerase II trigger liquid-liquid phase separation at double-strand breaks.

    Cell Reports 42, 113439, https://doi.org/10.1016/j.celrep.2023.113489

More publications Research Highlights archive

Reader’s Corner

literature to read, science to follow

In this section, a distinct selection of six highly stimulating research publications and reviews published during past 6 months is presented. It is our hope that links to exciting science, which deserves attention of the structural biology community, will help you to locate gems in the steadily expanding jungle of scientific literature. You are welcome to point out to any paper you found interesting by sending a link or citation to readerscorner@ciisb.org. The section is being updated regularly.


 

7 Dec 2023

Celebrating 30 years of Structure

Journal Structure was launched in 1993 as the first journal exclusively dedicated to structural biology by our founding academic chief editors, Wayne A. Hendrickson and Carl-Ivar Br€ande´ n, who were later joined by Alan Fersht. Christopher Lima and Andrej Sali became academic chief editors of Structure in 2003, and they were at the helm of the journal for 18 years until stepping down in the autumn 2021.

Structure is now celebrating its 30th birthday with this special anniversary issue. Editors commissioned reviews to highlight recent developments in different areas of structural biology. Sabine Botha and Petra Fromme provide an overview of the current state of serial femtosecond crystallography (SFX) research, the impact COVID-19 had on the SFX community, and how scientists adapted to these challenges. Koji Yonekura and his co-workers describe their contributions toward the development of electron 3D crystallography/microcrystal electron diffraction (MicroED) and highlight applications and current limitations of this method. Vaibhav KumarShukla, Gabriella Heller, and Flemming Hansen discuss the impact of artificial intelligence (AI) on biomolecular nuclear magnetic resonance (NMR) spectroscopy. Tuo Wang and his colleagues report how solid-state NMR is used to study the structures of fungaland plant cell walls. Syma Khalid and her co-workers define the term ‘‘computational microbiology’’ and describe state-of-the-art molecular dynamics imulations of bacterial systems.

21 Nov 2023

Intrinsic structural dynamics dictate enzymatic activity and inhibition (PNAS)

Enzymes are known to sample various conformations, many of which are critical for their biological function. However, structural characterizations of enzymes predominantly focus on the most populated conformation. As a result, single-point mutations often produce structures that are similar or essentially identical to those of the wild-type enzyme despite large changes in enzymatic activity. Here, we show for mutants of a histone deacetylase enzyme (HDAC8) that reduced enzymatic activities, reduced inhibitor affinities, and reduced residence times are all captured by the rate constants between intrinsically sampled conformations that, in turn, can be obtained independently by solution NMR spectroscopy. Thus, for the HDAC8 enzyme, the dynamic sampling of conformations dictates both enzymatic activity and inhibitor potency. Our analysis also dissects the functional role of the conformations sampled, where specific conformations distinct from those in available structures are responsible for substrate and inhibitor binding, catalysis, and product dissociation. Precise structures alone often do not adequately explain the effect of missense mutations on enzymatic activity and drug potency. Our findings not only assign functional roles to several conformational states of HDAC8 but they also underscore the paramount role of dynamics, which will have general implications for characterizing missense mutations and designing inhibitors.

Reader’s Corner Archive

Quote of February

“Scientists have become the bearers of the torch of discovery in our quest for knowledge.”

Stephen Hawking

https://ec.europa.eu/info/research-and-innovation/research-area/health-research-and-innovation/coronavirus-research-and-innovation/covid-research-manifesto_en

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