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; 1M0505 - Centre of targeted Therapeutics; extension period 2010-2001; 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 203/09/0820; Structure-assisted design of selective nucleotidase inhibitors; 2009-2013; J. Brynda - principal investigator
Ministry of Industry and Trade CR; 2A-2TP1/076 Generic therapeutic antibodies; 2007-2011; J. Sedlacek - principal investigator
FP6 EU; LSHP-CT-2007-037693; HIV protease inhibitor resistance by enzyme-substrate coevolution; 2007-spring 2010; J. Sedlacek - co-investigator

Most important recent papers

(2005-present; names of the lab members underlined)

Rezacova P, Brynda J, Lescar J, Fabry M, Horejsi M, Sieglova I, Sedlacek J, Bentley GA. Crystal structure of a cross-reaction complex between an anti-HIV-1 protease antibody and an HIV-2 protease peptide. J Struct Biol 149(3): 332-7, 2005. (Pubmed) (DOI)

Cigler P, Kozisek M, Rezacova P, Brynda J, Otwinowski Z, Pokorna J, Plesek J, Gruner B, Doleckova-Maresova L, Masa M, Sedlacek J, Bodem J, Krausslich HG, Kral V, Konvalinka J. From nonpeptide toward noncarbon protease inhibitors: metallacarboranes as specific and potent inhibitors of HIV protease. Proc Natl Acad Sci U S A 102(43): 15394-9, 2005. (Pubmed) (DOI)

Ondracek J, Weiss MS, Brynda J, Fiala J, Jursik F, Rezacova P, Jenner LB, Sedlacek J. Regular arrangement of periodates bound to lysozyme. Acta Crystallogr D Biol Crystallogr 61(Pt 9): 1181-9, 2005. (Pubmed) (DOI)

Ondracek J, Mesters JR. An ensemble of crystallographic models enables the description of novel bromate-oxoanion species trapped within a protein crystal. Acta Crystallogr D Biol Crystallogr 62(Pt 9): 996-1001, 2006. (Pubmed) (DOI)

Kozisek M, Bray J, Rezacova P, Saskova K, Brynda J, Pokorna J, Mammano F, Rulisek 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(4): 1005-16, 2007. (Pubmed) (DOI)

Kral V, Mader P, Collard R, Fabry M, Horejsi M, Rezacova P, Kozisek M, Zavada J, Sedlacek J, Rulisek 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 71(3): 1275-87, 2008. (Pubmed) (DOI)

Bartonova V, Kral V, Sieglova I, Brynda J, Fabry M, Horejsi M, Kozisek M, Saskova KG, Konvalinka J, Sedlacek J, Rezacova P. Potent inhibition of drug-resistant HIV protease variants by monoclonal antibodies. Antiviral Res 78(3): 275-7, 2008. (Pubmed) (DOI)

Saskova KG, Kozisek M, Lepsik M, Brynda J, Rezacova P, Vaclavikova J, Kagan RM, Machala L, Konvalinka J. Enzymatic and structural analysis of the I47A mutation contributing to the reduced susceptibility to HIV protease inhibitor lopinavir. Protein Sci 17(9): 1555-64, 2008. (Pubmed) (DOI)

Krejcirikova V, Fabry M, Markova V, Maly P, Rezacova P, Brynda J. Crystallization and preliminary X-ray diffraction analysis of mouse galectin-4 N-terminal carbohydrate recognition domain in complex with lactose. Acta Crystallogr Sect F Struct Biol Cryst Commun 64(Pt 7): 665-7, 2008. (Pubmed) (DOI)

Kozisek M, Cigler P, Lepsik M, Fanfrlik J, Rezacova P, Brynda J, Pokorna J, Plesek J, Gruner B, Grantz Saskova K, Vaclavikova J, Kral V, Konvalinka J. Inorganic polyhedral metallacarborane inhibitors of HIV protease: a new approach to overcoming antiviral resistance. J Med Chem 51(15): 4839-43, 2008. (Pubmed) (DOI)

Rezacova P, Kozisek M, Moy SF, Sieglova I, Joachimiak A, Machius M, Otwinowski Z. Crystal structures of the effector-binding domain of repressor Central glycolytic gene Regulator from Bacillus subtilis reveal ligand-induced structural changes upon binding of several glycolytic intermediates. Mol Microbiol 69(4): 895-910, 2008. (Pubmed) (DOI)

Kozisek M, Saskova KG, Rezacova P, Brynda J, van Maarseveen NM, De Jong D, Boucher CA, Kagan RM, Nijhuis M, Konvalinka J. Ninety-nine is not enough: molecular characterization of inhibitor-resistant human immunodeficiency virus type 1 protease mutants with insertions in the flap region. J Virol 82(12): 5869-78, 2008. (Pubmed) (DOI)

Rezacova P, Pokorna J, Brynda J, Kozisek M, Cigler P, Lepsik M, Fanfrlik J, Rezac J, Grantz Saskova K, Sieglova I, Plesek J, Sicha V, Gruner B, Oberwinkler H, Sedlacek J, Krausslich HG, Hobza P, Kral V, Konvalinka J. Design of HIV protease inhibitors based on inorganic polyhedral metallacarboranes. J Med Chem 52(22): 7132-41, 2009. (Pubmed) (DOI)

Saskova KG, Kozisek M, Rezacova P, Brynda J, Yashina T, Kagan RM, Konvalinka J. Molecular characterization of clinical isolates of human immunodeficiency virus resistant to the protease inhibitor darunavir. J Virol 83(17): 8810-8, 2009. (Pubmed) (DOI)

Dostal J, Brynda J, Hruskova-Heidingsfeldova O, Sieglova I, Pichova I, Rezacova P. The crystal structure of the secreted aspartic protease 1 from Candida parapsilosis in complex with pepstatin A. J Struct Biol 167(2): 145-52, 2009. (Pubmed) (DOI)

Wolfova J, Smatanova IK, Brynda J, Mesters JR, Lapkouski M, Kuty M, Natalello A, Chatterjee N, Chern SY, Ebbel E, Ricci A, Grandori R, Ettrich R, Carey J. Structural organization of WrbA in apo- and holoprotein crystals. Biochim Biophys Acta 1794(9): 1288-98, 2009. (Pubmed) (DOI)

Reviews

Rezacova P, Brynda J, Fabry M, Horejsi M, Stouracova R, Lescar J, Chitarra V, Riottot MM, Sedlacek J, Bentley GA. Inhibition of HIV protease by monoclonal antibodies. J Mol Recognit 15(5): 272-6, 2002. (Pubmed) (DOI)

Kratochvil B, Husak M, Brynda J, Sedlacek J. What can the current x-ray structure analysis offer? Chemické Listy 102: 889-901, 2008. (in Czech, English abstract)

Pokorna J, Machala L, Rezacova P, Konvalinka J. Current and Novel Inhibitors of HIV Protease. Viruses 1: 1209-39, 2009. (PDF)

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

Solving macromolecular 3D structures (Brynda, Řezáčová) - semestral course, Faculty of Science, Charles University