Research topics
HIV protease - structural studies of protease:inhibitor complexes; molecular design - recombinant formats of useful antibodies
Current grant support
Ministry of Education, Youth and Sports CR - OE210 Radionuclide-labelled protein-engineering antibodies, 2006-2009, J. Sedláček, international coordinator
Ministry of Education, Youth and Sports CR - 1M0505 Centre of targeted Therapeutics, 2005-2009, M. Fábry - co-investigator
Ministry of Education, Youth and Sports CR - LC06077 Centre of Chemical Genetics 2005-2009 J. Brynda - co-investigator
GA CR GA 301/07/0600 J. Brynda - co-investigator
GA CR GA 203/09/0820 (Structure-assisted design of selective nucleotidase inhibitors)
Ministry of Industry and Trade CR - 2A-2TP1/076 Generic therapeutic antibodies; J. Sedlacek
FP6 EU LSHP-CT-2007-037693 HIV protease inhibitor resistance by enzyme-substrate coevolution; J.Sedlacek
Most important recent papers
(2004-present; names of the lab members underlined)Brynda, J., Rezacova, P., Fabry, M., Horejsi, M., Stouracova, R., Soucek, M., Hradilek, M., Konvalinka, J., Sedlacek, J.: Inhibitor binding at the protein interface in crystals of a HIV 1 protease complex. Acta Crystallogr. D Biol. Crystallogr. 60: 1943-8, 2004. (PubMed)
Brynda, J., Rezacova, P., Fabry, M., Horejsi, M., Stouracova, R., Sedlacek, J., Soucek, M., Hradilek, M., Lepsik, M., Konvalinka, J.: A phenylnorstatine inhibitor binding to HIV-1 protease: geometry, protonation and subsite-pocket interactions analyzed at atomic resolution. J. Med. Chem. 47: 2030-6, 2004. (PubMed)
Rezacova, P., Brynda, J., Lescar, J., Fabry, M., Horejsi, M., Sieglova, I., Sedlacek, J., Bentley, G.A.: Crystal structure of a cross-reaction complex between an anti-HIV-1 protease antibody and an HIV-2 protease peptide. J. Struct. Biol. 149: 332-7, 2005. (PubMed)
Cígler, P., Koľíšek, M., Řezáčová, P., Brynda, J., Otwinowski, Z., Pokorná, J., Plešek, J., Grüner, B., Dolečková-Marešová, L., Máša, M., Sedláček, J., Bodem, J., Kraeusslich, H.-G., Král, V., Konvalinka, J.: From non-peptide towards non-carbon protease inhibitors: metallacarboranes as specific and potent inhibitors of HIV protease. Proc. Natl. Acad. Sci. USA 102: 15394-9, 2005. (PubMed)
Ondráček, J., Weiss, M.S., Brynda, J., Fiala, J., Jursík, F., Řezáčová, P., Jenner, L.B., Sedláček, J.: Regular arrangement of periodates bound to lysozyme. Acta Crystallogr. D. Biol. Crystallogr. 61: 1181-1189, 2005. (PubMed)
Duskova, J., Dohnalek, J., Skalová, T., Petroková, H., Vondracková, E., Hradilek, M., Konvalinka, J., Soucek, M., Brynda, J., Fabry, M., Sedlacek, J., Hasek, J.: On the role of the R configuration of the reaction-intermediates isostere in HIV-1 protease-inhibitor binding: X-ray structure at 2.0 A resolution. Acta Crystallogr. D Biol. Crystallogr. 62 (Pt 5): 489-497, 2006. (PubMed)
Markova, V., Smetana, Jr. K., Jenikova, G., Lachova, J., Krejcirikova, V., Poplstein, M., Fabry, M., Brynda, J., Alvarez, R. A., Cummings, R. D., Maly, P.: Role of the carbohydrate recognition domains of mouse galectin-4 and galectin-6 in mouse cells and tissues. Int. J. Mol. Med. 18: 65-76, 2006. (PubMed)
Ondracek, J., Mesters, J.R.: An ensemble of crystallographic models enables the description of novel bromate-oxonian species trapped within a protein crystal. Acta Crystallogr. D Biol. Crystallogr. 69 (Pt 9): 996-1001, 2006. (PubMed)
Carey, J., Brynda, J., Wolfova, J., Grandori, R., Gustavsson, T., Ettrich, R., Smatanova, I.K.: WrbA bridges bacterial flavodoxins and eukaryotic NAD(P)H:quinone oxidoreductases. J. Protein Sci. 16: 2301-5, 2007. (PubMed)
Wolfova, J., Mesters, J.R., Brynda, J., Grandori, R., Natalello, A., Carey, J., Kuta Smatanova, I.: Crystallization and preliminary diffraction analysis of Escherichia coli WrbA in complex with its cofactor flavin mononucleotide. Acta Crystallogr. Sect. F-Struct. Biol. Cryst Commun. 63, 571-575, 2007. (PubMed)
Kožíšek, M., Bray, J., Řezáčová, P., Šašková, K., Brynda, J., Pokorná, J., Mammano, F., Rulíšek, L., Konvalinka, J.: Molecular analysis of the HIV-1 resistance development: enzymatic activities, crystal structures, and thermodynamics of nelfinavir-resistant HIV protease mutants. J. Mol. Biol. 374: 1005-16, 2007. (PubMed)
Král, V., Mader, P., Collard, R., Fábry, M., Hořejší, M., Řezáčová, P., Kožíšek, M., Závada, J., Sedláček, J., Rulíšek, L., Brynda, J.: Stabilization of antibody structure upon association to a human carbonic anhydrase IX epitope studied by X-ray crystallography, microcalorimetry, and molecular dynamics simulations. Proteins. Epub Nov 27, 2007. (PubMed)
Bartoňová V., Král V., Sieglová I., Brynda J., Fábry M., Hořejší M., Kožíšek M., Šašková K.G., Konvalinka J., Sedláček J., Řezáčová P.: Potent inhibition of drug-resistant HIV protease variants by monoclonal antibodies. Antiviral Res. Epub Feb 20, 2008. (PubMed)
Gratz-Šašková K., Kožíšek M., Lepšík M., Brynda J., Řezáčová P., Václavíková J., Kagan R.M., Machala, L., Konvalinka, J. Enzymatic and structural analysis of the I47A mutation contributing to the reduced susceptibility to HIV protease inhibitor lopinavir. Protein Science 17: 1555-64, 2008. (PubMed)
Krejčiříková V., Fábry M., Marková V., Malý P., Řezáčová P., Brynda J. Crystallization and preliminary X-ray diffraction analysis of mouse galectin-4 N-terminal carbohydrate recognition domain in complex with lactose. Acta Crystallographica F 64: 665-7, 2008. (PubMed)
Kožíšek M., Cígler P., Lepšík M., Fanfrlík J., Řezáčová P., Brynda J., Pokorná J., Plešek J., Grüner B., Grantz-Šašková K., Václavíková J., Kraeusslich H.-G., Král V., Konvalinka J. Inorganic polyhedral metallacarborane scaffolds - a new approach to overcoming resistance to HIV protease inhibitors. Journal of Medicinal Chemistry 51: 4839-43, 2008. (PubMed)
Řezáčová P., Kožíšek M., Moy S.F., Sieglová I., Joachimiak A., Machius M., Otwinowski Z.: Crystal structures of the effector-binding domain of repressor CggR from Bacillus subtilis reveal ligand-induced structural changes upon binding of several glycolytic intermediates. Molecular Microbiology 69: 895-910, 2008. (PubMed)
Kožíšek M., Šašková K., Řezáčová P., Brynda J., van Maarseveen N.M., De Jong D., Boucher Ch., Kagan R., Nijhuis M., Konvalinka J.: Ninety Nine is Not Enough: Molecular Characterisation of Drug-Resistant HIV-Protease Mutants with Insertions in the Flap Region Yielding Resistance to Protease Inhibitors. Journal of Virology 82: 5869-5878, 2008. (PubMed)
Fanfrlik J, Brynda J, Rezac J, Hobza P, Lepsik M. Interpretation of Protein/Ligand Crystal Structure using QM/MM Calculations: Case of HIV-1 Protease/Metallacarborane Complex. J Phys Chem B. 112 (47): 15094-15102, 2008. (PubMed)
Reviews
Rezacova, P., Brynda, J., Fabry, M., Horejsi, M., Stouracova, R., Lescar, J., Chitarra, V., Riottot, M.-M., Sedlacek, J., Bentley, G. A..: Inhibition of HIV protease by monoclonal antibodies. J. Mol. Recognit. 15: 272-276, 2002. (PubMed)
Other results
HipHop refinement method & programs for protein crystallography, http://www.img.cas.cz/hiphop
X-Ray Station
Heart of Europe bio-Crystallography Meeting
Teaching, lectures, public presentations
Semestral course, Charles University, Faculty of Science: Solving Macromolecular 3D Structures (Brynda, Řezáčová) (link)