http://www.biomed.cas.cz/d312/index.php?section=home
Our group is focused on structural biology (the relationship between the structure and function of certain groups of proteins), particularly we focus on the proteins which participate in the signal transmission in the cell. Among methods we use are recombinant protein expression, biophysical characterization, study of intermolecular interactions, protein structure and interaction surfaces. All these methods enable us to better understand the details how the activity and function of protein-protein complexes is regulated. Our research is focused mainly on:
- Structural biology of 14-3-3 proteins and their complexes
- Mechanism of regulation of proteinkisases CaMKK1, CaMKK2 and ASK1
- Study of inhibition of protease caspase-2 by 14-3-3 protein
- Study of DNA-binding domain of transcription factor FOXO4
Projects
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Phosducin (Pdc), a highly conserved phosphoprotein, plays an important role in the regulation of G-protein signalling, transcriptional control, and modulation of blood pressure. Pdc is negatively regulated by phosphorylation followed by binding to the 14-3-3 protein.
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Our results show the activation of yeast neutral trehalase Nth1 by 14-3-3 proteins from the structural point of view. Our data could be important for understanding of the activation process of Nth1 as well as of the role of 14-3-3 proteins in the regulation of other enzymes.
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Achievements
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Kacirova M, Kosek D, Kadek A, Man P, Vecer J, Herman P, Obsilova V and Obsil T
J. Biol. Chem. jbc.M115.636563. First Published on May 13, 2015, doi:10.1074/jbc.M115.636563
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Prof. RNDr. Tomáš Obšil, Ph.D. was awarded by the title of professor at The Faculty of Science, Charles University, majoring in Physical Chemistry. Professors graduation will take place December 18, 2014.
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Kopecka M, Kosek D, Kukacka Z, Rezabkova L, Man P, Novak P, Obsil T, Obsilova V.
J Biol Chem. 2014 May 16;289(20):13948-61.
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Publications
Kirubakaran, P. - Pfeiferová, L. - Boušová, Kristýna - Bednárová, L. - Obšilová, Veronika - Vondrášek, J.
Artificial proteins as allosteric modulators of PDZ3 and SH3 in two-domain constructs: A computational characterization of novel chimeric proteins
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Proteins-Structure, Function and Bioinformatics. 2016, roč. 84, 10, p. 1358-1374
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IF = 2.397
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Petrvalská, Olivia - Košek, Dalibor - Kukačka, Zdeněk - Tošner, Z. - Man, Petr - Večeř, J. - Herman, P. - Obšilová, Veronika - Obšil, Tomáš
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Structural Insight into the 14-3-3 Protein-dependent Inhibition of Protein Kinase ASK1 (Apoptosis Signal-regulating kinase 1)
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Journal of Biological Chemistry. 2016, roč. 291, 39, p. 20753-20765
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IF = 4.125
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Jirků, Michaela - Lánský, Zdeněk - Bednárová, L. - Šulc, Miroslav - Monincová, L. - Majer, P. - Vyklický ml., Ladislav - Vondrášek, J. - Teisinger, Jan - Boušová, Kristýna
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The characterization of a novel S100A1 binding site in the N-terminus of TRPM1
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International Journal of Biochemistry and Cell Biology. 2016, roč. 78, Sep 2016, p. 186-193
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IF = 3.505
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Kylarová, Salome - Košek, Dalibor - Petrvalská, Olivia - Pšenáková, Katarína - Man, Petr - Večeř, J. - Herman, P. - Obšilová, Veronika - Obšil, Tomáš
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Cysteine residues mediate high‐affinity binding of thioredoxin to ASK1
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FEBS Journal. 2016, roč. 283, 20, p. 3821-3838
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IF = 3.902
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Jirků, Michaela - Bumba, Ladislav - Bednárová, Lucie - Kubala, M. - Šulc, Miroslav - Franěk, M. - Vyklický ml., Ladislav - Vondrášek, Jiří - Teisinger, Jan - Boušová, Kristýna
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Characterization of the part of N-terminal PIP2 binding site of the TRPM1 channel
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Biophysical Chemistry. 2015, Vol. 207, Dec, p. 135-142
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IF = 2.363
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Kacířová, Miroslava - Košek, Dalibor - Kádek, Alan - Man, Petr - Večeř, J. - Herman, P. - Obšilová, Veronika - Obšil, Tomáš
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Structural Characterization of Phosducin and Its Complex with the 14-3-3 Protein
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Journal of Biological Chemistry. 2015, Vol. 290, 26, p. 16246-16260
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IF = 4.258
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Boušová, Kristýna - Jirků, Michaela - Bumba, Ladislav - Bednárová, Lucie - Šulc, Miroslav - Franěk, M. - Vyklický ml., Ladislav - Vondrášek, Jiří - Teisinger, Jan
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PIP2 and PIP3 interact with N-terminus region of TRPM4 channel
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Biophysical Chemistry. 2015, Vol. 205, Oct 2015, p. 24-32
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IF = 2.363
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Gryčová, Lenka - Holendová, Blanka - Lánský, Zdeněk - Bumba, Ladislav - Jirků, Michaela - Boušová, Kristýna - Teisinger, Jan
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Ca2+ Binding Protein S100A1 Competes with Calmodulin and PIP2 for Binding Site on the C-Terminus of the TPRV1 Receptor
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ACS Chemical Neuroscience. 2015, Vol. 6, 3, p. 386-392
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IF = 4.348
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Obšilová, Veronika - Kopecká, Miroslava - Košek, Dalibor - Kacířová, M. - Kylarová, Salome - Řežábková, L. - Obšil, T.
Mechanisms of the 14-3-3 protein function: regulation of protein function through conformational modulation
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Physiological Research 2014, roč. 63, suppl.1, s155-s164. ISSN 0862-8408.
IF = 1.293
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Košek, Dalibor - Kylarová, Salome - Pšenáková, Katarína - Řežábková, L. - Herman, P. - Večeř, J. - Obšilová, Veronika - Obšil, T.
Biophysical and Structural Characterization of the Thioredoxin-binding Domain of Protein Kinase ASK1 and Its Interaction with Reduced Thioredoxin
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Journal of Biological Chemistry 2014, roč. 289, 35, p. 24463-24474. ISSN 0021-9258.
IF = 4.573
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Superpozice ab inicio molekulární obálky získané ze SAXS měření s teoretickým modelem ASK1-TBD:TRX1 komplexu. Kosek et al. (2014).
A) Identifikace klíčových fosforylačních míst zodpovědných za aktivaci neutrální trehalasy Nth1 proteinem Bmh1. B) Pokles kinetiky výměny vodíku za deuterium indukované vazbou proteinu Bmh1 pro peptid zahrnující vápníkovou doménu, který se nachází na vazebném rozhraní obou proteinů. C) Struktura s nízkým rozlišením komplexu Nth1:Bmh1 získaná z měření maloúhlového rozptylu světla SAXS. Veisova et al. (2012), Macakova et al. (2013), Kopecka et al. (2014).
Protein 14-3-3 interaguje s N- i C-koncovými Gtβγ vazebnými rozhraními fosducinu. Kacirova et al. (2015).
