Strukturní biologie a charakterizace vztahů mezi strukturou a funkcí medicínsky významných proteinů
Laboratoř strukturní biologie
Vedoucí laboratoře: RNDr. Cyril Bařinka, Ph.D.
1. Glutamát karboxypeptidasa II (GCPII) – strukturní charakterizace a vývoj nových ligandů a technik cílených na GCPII a její ortology/paralogy.
2. Histon deacetylasy (HDACs) – charakterizace vztahu struktura-funkce a rentgenostrukturní analýza
Laboratoř rovněž aktivně spolupracuje s dalšími vědeckými skupinami a při společných projektech využíváme portfolio metod, které jsou v naší laboratory zavedené. Mezi tyto techniky patří heterologní exprese proteinů v nejrůznějších systémech (E.coli, K.lactis, P.pastoris, hmyzí S2 a Hi5 buňky, savčí buňky), enzymatická a fyzikálně-chemická charakterizace purifikovaných proteinů, včetně robotického testování krystalizačních podmínek a řešení krystalových struktur cílových molekul.
2022
-
Novakova, Z., Mikesova, J., Ondrakova, M., Kutil, Z., Vesela, K., Martasek, P., Barinka, C. (2022). "Molecular characterization of a novel His333Arg variant of human protoporphyrinogen oxidase IX." Biochem Biophys Res Commun, 588, 182-186. https://doi.org/10.1016/j.bbrc.2021.12.062 (ASEP)
2021
- Awad, M., Nedvedova, J., Nedved, O. (2021)."Thermal plasticity of antioxidative activity in fresh adults of Harmonia axyridis (Coleoptera: Coccinellidae)." African Entomology, 29(1), 125-132. https://doi.org/10.4001/003.029.0125
-
Jenickova, I., Kasparek, P., Petrezselyova, S., Elias, J., Prochazka, J., Kopkanova, J., Navratil, M., Barinka, C., Sedlacek, R. (2021). "Efficient allele conversion in mouse zygotes and primary cells based on ele ctroporation of Cre protein." Methods, 191 (87-94). https://doi.org/10.1016/j.ymeth.2020.07.005
-
Zessin, M., Meleshin, M., Simic, Z., Kalbas, D., Arbach, M., Gebhardt, P., Melesina, J., Liebscher, S., Bordusa, F., Sippl, W., Barinka, C., & Schutkowski, M. (2021, Oct 12). Continuous Sirtuin/HDAC (histone deacetylase) activity assay using thioamides as PET (Photoinduced Electron Transfer)-based fluorescence quencher. Bioorg Chem, 117, 105425. https://doi.org/10.1016/j.bioorg.2021.105425
-
Zhang, J., Rakhimbekova, A., Duan, X., Yin, Q., Foss, C. A., Fan, Y., Xu, Y., Li, X., Cai, X., Kutil, Z., Wang, P., Yang, Z., Zhang, N., Pomper, M. G., Wang, Y., Barinka, C., & Yang, X. (2021, Sep 15). A prostate-specific membrane antigen activated molecular rotor for real-time fluorescence imaging. Nature Communications, 12(1), 5460. https://doi.org/10.1038/s41467-021-25746-6
2020
- Cardinale, J., Roscher, M., Schaefer, M., Geerlings, M., Benesova, M., Bauder-Wust, U., Remde, Y., Eder, M., Novakova, Z., Motlova, L., Barinka, C., Giesel, F. L., & Kopka, K. (2020). "Development of PSMA-1007 - Related Series of (18)F-Labeled Glu-ureido type PSMA inhibitors." J Med Chem.
-
Hapuarachchige, S., C. T. Huang, M. C. Donnelly, C. Barinka, S. E. Lupold, M. G. Pomper and D. Artemov (2020). "Cellular Delivery of Bioorthogonal Pretargeting Therapeutics in PSMA-Positive Prostate Cancer." Mol Pharm 17(1): 98-108.
-
Henrichs, V., Grycova, L., Barinka, C., Nahacka, Z., Neuzil, J., Diez, S., Rohlena, J., Braun, M., Lansky, Z. (2020). "Mitochondria-adaptor TRAK1 promotes kinesin-1 driven transport in crowded environments." Nature Communications, 11(1), 3123
-
Huang, C. T., Guo, X., Barinka, C., Lupold, S. E., Pomper, M. G., Gabrielson, K., Raman, V., Artemov, D., & Hapuarachchige, S. (2020). Development of 5D3-DM1: A Novel Anti-Prostate-Specific Membrane Antigen Antibody-Drug Conjugate for PSMA-Positive Prostate Cancer Therapy. Mol Pharm, 17(9), 3392-3402/p>
-
Kim, K., H. Kwon, C. Barinka, L. Motlova, S. Nam, D. Choi, H. Ha, H. Nam, S. H. Son, I. Minn, M. G. Pomper, X. Yang, Z. Kutil and Y. Byun (2020). "Novel beta- and gamma-Amino Acid-Derived Inhibitors of Prostate-Specific Membrane Antigen." J Med Chem.
-
Novakova, Z., Belousova, N., Foss, C. A., Havlinova, B., Gresova, M., Das, G., Lisok, A., Prada, A., Barinkova, M., Hubalek, M., Pomper, M. G., & Barinka, C. (2020). "Engineered Fragments of the PSMA-Specific 5D3 Antibody and Their Functional Characterization." Int J Mol Sci, 21(18).
- Ptacek, J., Zhang, D., Qiu, L., Kruspe, S., Motlova, L., Kolenko, P., Novakova, Z., Shubham, S., Havlinova, B., Baranova, P., Chen, S. J., Zou, X., Giangrande, P., & Barinka, C. (2020). "Structural basis of prostate-specific membrane antigen recognition by the A9g RNA aptamer." Nucleic Acids Research, 48(19), 11130-11145.
-
Shen, S., M. Svoboda, G. Zhang, M. A. Cavasin, L. Motlova, T. A. McKinsey, J. H. Eubanks, C. Barinka and A. P. Kozikowski (2020). "Structural and in Vivo Characterization of Tubastatin A, a Widely Used Histone Deacetylase 6 Inhibitor." ACS Med Chem Lett 11(5): 706-712.
-
Ustinova, K., Z. Novakova, M. Saito, M. Meleshin, J. Mikesova, Z. Kutil, P. Baranova, B. Havlinova, M. Schutkowski, P. Matthias and C. Barinka (2020). "The disordered N-terminus of HDAC6 is a microtubule-binding domain critical for efficient tubulin deacetylation." J Biol Chem.
2019
-
Banerjee, S. R., V. Kumar, A. Lisok, D. Plyku, Z. Novakova, M. Brummet, B. Wharram, C. Barinka, R. Hobbs and M. G. Pomper (2019). "Evaluation of (111)In-DOTA-5D3, a Surrogate SPECT Imaging Agent for Radioimmunotherapy of Prostate-Specific Membrane Antigen." J Nucl Med 60(3): 400-406.
-
Barinka, C., Z. Novakova, N. Hin, D. Bim, D. V. Ferraris, B. Duvall, G. Kabarriti, R. Tsukamoto, M. Budesinsky, L. Motlova, C. Rojas, B. S. Slusher, T. A. Rokob, L. Rulisek and T. Tsukamoto (2019). "Structural and computational basis for potent inhibition of glutamate carboxypeptidase II by carbamate-based inhibitors." Bioorg Med Chem 27(2): 255-264.
-
Knox, T., E. Sahakian, D. Banik, M. Hadley, E. Palmer, S. Noonepalle, J. Kim, J. Powers, M. Gracia-Hernandez, V. Oliveira, F. Cheng, J. Chen, C. Barinka, J. Pinilla-Ibarz, N. H. Lee, A. Kozikowski and A. Villagra (2019). "Selective HDAC6 inhibitors improve anti-PD-1 immune checkpoint blockade therapy by decreasing the anti-inflammatory phenotype of macrophages and down-regulation of immunosuppressive proteins in tumor cells." Sci Rep 9(1): 6136.
-
Kozikowski, A. P., S. Shen, M. Pardo, M. T. Tavares, D. Szarics, V. Benoy, C. A. Zimprich, Z. Kutil, G. Zhang, C. Barinka, M. B. Robers, L. Van Den Bosch, J. H. Eubanks and R. S. Jope (2019). "Brain Penetrable Histone Deacetylase 6 Inhibitor SW-100 Ameliorates Memory and Learning Impairments in a Mouse Model of Fragile X Syndrome." ACS Chem Neurosci 10(3): 1679-1695.
-
Kutil, Z., J. Mikesova, M. Zessin, M. Meleshin, Z. Novakova, G. Alquicer, A. Kozikowski, W. Sippl, C. Barinka and M. Schutkowski (2019). "Continuous Activity Assay for HDAC11 Enabling Reevaluation of HDAC Inhibitors." ACS Omega 4(22): 19895-19904.
-
Kutil, Z., L. Skultetyova, D. Rauh, M. Meleshin, I. Snajdr, Z. Novakova, J. Mikesova, J. Pavlicek, M. Hadzima, P. Baranova, B. Havlinova, P. Majer, M. Schutkowski and C. Barinka (2019). "The unraveling of substrate specificity of histone deacetylase 6 domains using acetylome peptide microarrays and peptide libraries." FASEB J 33(3): 4035-4045.
-
Shen, S., M. Hadley, K. Ustinova, J. Pavlicek, T. Knox, S. Noonepalle, M. T. Tavares, C. A. Zimprich, G. Zhang, M. B. Robers, C. Barinka, A. P. Kozikowski and A. Villagra (2019). "Discovery of a New Isoxazole-3-hydroxamate-Based Histone Deacetylase 6 Inhibitor SS-208 with Antitumor Activity in Syngeneic Melanoma Mouse Models." J Med Chem 62(18): 8557-8577.
-
Tishchenko, G., Morganti, P., Stoller, M., Kelnar, I., Mikešová, J., Kovářová, J., Hašek, J., Kužel, R., Netopilík, M., Kaprálková, L., Špírková, M., Pavlova, E., Chánová, E., Brožová, L., Pekárek, M., Kobera, L., Sedláková, Z., Kubies, D. (2019). Chitin nanofibrils-chitosan composite films: characterization and properties. Bionanotechnology to save the environment. Plant and fishery's biomass as alternative to petrol. P. Morganti. Basel: 191-226.
-
Wu, H., K. Yang, Z. Zhang, E. D. Leisten, Z. Li, H. Xie, J. Liu, K. A. Smith, Z. Novakova, C. Barinka and W. Tang (2019). "Development of Multifunctional Histone Deacetylase 6 Degraders with Potent Antimyeloma Activity." J Med Chem 62(15): 7042-7057.
-
Zessin, M., Z. Kutil, M. Meleshin, Z. Novakova, E. Ghazy, D. Kalbas, M. Marek, C. Romier, W. Sippl, C. Barinka and M. Schutkowski (2019). "One-Atom Substitution Enables Direct and Continuous Monitoring of Histone Deacylase Activity." Biochemistry 58(48): 4777-4789.
2018
-
Kutil, Z., Z. Novakova, M. Meleshin, J. Mikesova, M. Schutkowski and C. Barinka (2018). "Histone Deacetylase 11 Is a Fatty-Acid Deacylase." ACS Chem Biol 13(3): 685-693.
-
Nakajima, R., Z. Novakova, W. Tueckmantel, L. Motlova, C. Barinka and A. P. Kozikowski (2018). "2-Aminoadipic Acid-C(O)-Glutamate Based Prostate-Specific Membrane Antigen Ligands for Potential Use as Theranostics." ACS Med Chem Lett 9(11): 1099-1104.
-
Porter, N. J., S. Shen, C. Barinka, A. P. Kozikowski and D. W. Christianson (2018). "Molecular Basis for the Selective Inhibition of Histone Deacetylase 6 by a Mercaptoacetamide Inhibitor." ACS Med Chem Lett 9(12): 1301-1305.
-
Ptacek, J., J. Nedvedova, M. Navratil, B. Havlinova, J. Konvalinka and C. Barinka (2018). "The calcium-binding site of human glutamate carboxypeptidase II is critical for dimerization, thermal stability, and enzymatic activity." Protein Sci 27(9): 1575-1584.
2017
-
Kopka, K., M. Benesova, C. Barinka, U. Haberkorn and J. Babich (2017). "Glu-Ureido-Based Inhibitors of Prostate-Specific Membrane Antigen: Lessons Learned During the Development of a Novel Class of Low-Molecular-Weight Theranostic Radiotracers." J Nucl Med 58(Suppl 2): 17S-26S.
-
Lv, W., G. Zhang, C. Barinka, J. H. Eubanks and A. P. Kozikowski (2017). "Design and Synthesis of Mercaptoacetamides as Potent, Selective, and Brain Permeable Histone Deacetylase 6 Inhibitors." ACS Med Chem Lett 8(5): 510-515.
-
Novakova, Z., C. A. Foss, B. T. Copeland, V. Morath, P. Baranova, B. Havlinova, A. Skerra, M. G. Pomper and C. Barinka (2017). "Novel Monoclonal Antibodies Recognizing Human Prostate-Specific Membrane Antigen (PSMA) as Research and Theranostic Tools." Prostate 77(7): 749-764.
-
Rais, R., J. Vavra, T. Tichy, R. P. Dash, A. J. Gadiano, L. Tenora, L. Monincova, C. Barinka, J. Alt, S. C. Zimmermann, C. E. Slusher, Y. Wu, K. Wozniak, P. Majer, T. Tsukamoto and B. S. Slusher (2017). "Discovery of a para-Acetoxy-benzyl Ester Prodrug of a Hydroxamate-Based Glutamate Carboxypeptidase II Inhibitor as Oral Therapy for Neuropathic Pain." J Med Chem 60(18): 7799-7809.
-
Skultetyova, L., K. Ustinova, Z. Kutil, Z. Novakova, J. Pavlicek, J. Mikesova, D. Trapl, P. Baranova, B. Havlinova, M. Hubalek, Z. Lansky and C. Barinka (2017). "Human histone deacetylase 6 shows strong preference for tubulin dimers over assembled microtubules." Sci Rep 7(1): 11547.
-
Tavares, M. T., S. Shen, T. Knox, M. Hadley, Z. Kutil, C. Barinka, A. Villagra and A. P. Kozikowski (2017). "Synthesis and Pharmacological Evaluation of Selective Histone Deacetylase 6 Inhibitors in Melanoma Models." ACS Med Chem Lett 8(10): 1031-1036.
2016
-
Barinka, C., J. Ptacek, A. Richter, Z. Novakova, V. Morath and A. Skerra (2016). "Selection and characterization of Anticalins targeting human prostate-specific membrane antigen (PSMA)." Protein Eng Des Sel 29(3): 105-115.
-
Bumba, L., J. Masin, P. Macek, T. Wald, L. Motlova, I. Bibova, N. Klimova, L. Bednarova, V. Veverka, M. Kachala, D. I. Svergun, C. Barinka and P. Sebo (2016). "Calcium-Driven Folding of RTX Domain beta-Rolls Ratchets Translocation of RTX Proteins through Type I Secretion Ducts." Mol Cell 62(1): 47-62.
-
Conway, R. E., C. Rojas, J. Alt, Z. Novakova, S. M. Richardson, T. C. Rodrick, J. L. Fuentes, N. H. Richardson, J. Attalla, S. Stewart, B. Fahmy, C. Barinka, M. Ghosh, L. H. Shapiro and B. S. Slusher (2016). "Prostate-specific membrane antigen (PSMA)-mediated laminin proteolysis generates a pro-angiogenic peptide." Angiogenesis 19(4): 487-500.
-
Dannoon, S., T. Ganguly, H. Cahaya, J. J. Geruntho, M. S. Galliher, S. K. Beyer, C. J. Choy, M. R. Hopkins, M. Regan, J. E. Blecha, L. Skultetyova, C. R. Drake, S. Jivan, C. Barinka, E. F. Jones, C. E. Berkman and H. F. VanBrocklin (2016). "Structure-Activity Relationship of (18)F-Labeled Phosphoramidate Peptidomimetic Prostate-Specific Membrane Antigen (PSMA)-Targeted Inhibitor Analogues for PET Imaging of Prostate Cancer." J Med Chem 59(12): 5684-5694.
-
Novakova, Z., K. Wozniak, A. Jancarik, R. Rais, Y. Wu, J. Pavlicek, D. Ferraris, B. Havlinova, J. Ptacek, J. Vavra, N. Hin, C. Rojas, P. Majer, B. S. Slusher, T. Tsukamoto and C. Barinka (2016). "Unprecedented Binding Mode of Hydroxamate-Based Inhibitors of Glutamate Carboxypeptidase II: Structural Characterization and Biological Activity." J Med Chem 59(10): 4539-4550.
-
Novakova, Z., J. Cerny, C. J. Choy, J. R. Nedrow, J. K. Choi, J. Lubkowski, C. E. Berkman and C. Barinka (2016). "Design of composite inhibitors targeting glutamate carboxypeptidase II: the importance of effector functionalities." FEBS J 283(1): 130-143.
2015
-
Ganguly, T., S. Dannoon, M. R. Hopkins, S. Murphy, H. Cahaya, J. E. Blecha, S. Jivan, C. R. Drake, C. Barinka, E. F. Jones, H. F. VanBrocklin and C. E. Berkman (2015). "A high-affinity [(18)F]-labeled phosphoramidate peptidomimetic PSMA-targeted inhibitor for PET imaging of prostate cancer." Nucl Med Biol 42(10): 780-787.
-
Tykvart, J., C. Barinka, M. Svoboda, V. Navratil, R. Soucek, M. Hubalek, M. Hradilek, P. Sacha, J. Lubkowski and J. Konvalinka (2015). "Structural and biochemical characterization of a novel aminopeptidase from human intestine." J Biol Chem 290(18): 11321-11336.
-
Youn, S., K. I. Kim, J. Ptacek, K. Ok, Z. Novakova, Y. Kim, J. Koo, C. Barinka and Y. Byun (2015). "Carborane-containing urea-based inhibitors of glutamate carboxypeptidase II: Synthesis and structural characterization." Bioorg Med Chem Lett 25(22): 5232-5236.
2014
-
Navratil, M., J. Ptacek, P. Sacha, J. Starkova, J. Lubkowski, C. Barinka and J. Konvalinka (2014). "Structural and biochemical characterization of the folyl-poly-gamma-l-glutamate hydrolyzing activity of human glutamate carboxypeptidase II." FEBS J 281(14): 3228-3242.
-
Pavlicek, J., J. Ptacek, J. Cerny, Y. Byun, L. Skultetyova, M. G. Pomper, J. Lubkowski and C. Barinka (2014). "Structural characterization of P1'-diversified urea-based inhibitors of glutamate carboxypeptidase II." Bioorg Med Chem Lett 24(10): 2340-2345.
-
Tykvart, J., V. Navratil, F. Sedlak, E. Corey, M. Colombatti, G. Fracasso, F. Koukolik, C. Barinka, P. Sacha and J. Konvalinka (2014). "Comparative analysis of monoclonal antibodies against prostate-specific membrane antigen (PSMA)." Prostate 74(16): 1674-1690.
2012
-
Alquicer, G., D. Sedlak, Y. Byun, J. Pavlicek, M. Stathis, C. Rojas, B. Slusher, M. G. Pomper, P. Bartunek and C. Barinka (2012). "Development of a high-throughput fluorescence polarization assay to identify novel ligands of glutamate carboxypeptidase II." J Biomol Screen 17(8): 1030-1040.
-
Barinka, C., C. Rojas, B. Slusher and M. Pomper (2012). "Glutamate carboxypeptidase II in diagnosis and treatment of neurologic disorders and prostate cancer." Curr Med Chem 19(6): 856-870.
-
Pavlicek, J., J. Ptacek and C. Barinka (2012). "Glutamate carboxypeptidase II: an overview of structural studies and their importance for structure-based drug design and deciphering the reaction mechanism of the enzyme." Curr Med Chem 19(9): 1300-1309.
-
Tykvart, J., P. Sacha, C. Barinka, T. Knedlik, J. Starkova, J. Lubkowski and J. Konvalinka (2012). "Efficient and versatile one-step affinity purification of in vivo biotinylated proteins: expression, characterization and structure analysis of recombinant human glutamate carboxypeptidase II." Protein Expr Purif 82(1): 106-115.
2011
-
Plechanovova, A., Y. Byun, G. Alquicer, L. Skultetyova, P. Mlcochova, A. Nemcova, H. J. Kim, M. Navratil, R. Mease, J. Lubkowski, M. Pomper, J. Konvalinka, L. Rulisek and C. Barinka (2011). "Novel substrate-based inhibitors of human glutamate carboxypeptidase II with enhanced lipophilicity." J Med Chem 54(21): 7535-7546.
2010
-
Zhang, A. X., R. P. Murelli, C. Barinka, J. Michel, A. Cocleaza, W. L. Jorgensen, J. Lubkowski and D. A. Spiegel (2010). "A remote arene-binding site on prostate specific membrane antigen revealed by antibody-recruiting small molecules." J Am Chem Soc 132(36): 12711-12716.
Patents
- Skerra, A. R., A.; Morath, V.; Barinka, C.; Ptacek, J. ( 2019). US10406247. PSMA-Specific Binding Proteins., Technische Universität München (DE); Biotechnologický ústav AVCR, v.v.i. (CZ).
GAČR: GJ19-22269Y, Kutil: Nové inhibitory glutamát karboxypeptidasy II: studie vztahu struktura-aktivita a funkční testování. 2019-2021.
MŠMT: LTAUSA18196, Nováková: Vývoj nástrojů pro diagnostiku a terapii rakoviny prostaty na bázi rekombinantních derivátů protilátek. 2019-2022.
GAČR: GA18-04790S, Bařinka: Proteinové inženýrství monoklonálních protilátek využitelných pro diagnostiku a terapii nádorů. 2018-2020.
GAČR: GA18-14167S, Bařinka: Orthologní glutamát karboxypeptidázy 2 v modelových organizmech - hledání fyziologických rolí a terapeutického potenciálu enigmatického enzymu. 2018-2020.
AZV: NV17-32727A, Bařinka: Inovativní strategie pro personalizovanou medicínu: molekulární přístupy cílené na vliv dědičných metabolických chorob způsobených mutacemi v PPO. 2017-2020.
Středočeské inovační vouchery: Poskytnutí znalostí firmě Apronex s.r.o. 2016.
GAČR: GA15-19640S, Bařinka: Substrátová specifita histon deacetylasy 6 na molekulární úrovni. 2015-2017.
MŠMT (program OP VK): CZ.1.07/2.3.00/30.0045, Bařinka, Nováková, Kubista, Valihrach, Hejnalová: Biotechnologický expert v oblasti strukturní biologie a genové exprese. 2012-2015.
GAČR: GAP301/12/1513, Bařinka: Vysokoafinitní ligandy použitelné k detekci nádorů. 2012-2016.
EMBO: ASTF 56 – 2012, Bařinka: Short-Term Fellowship. 2012.
MŠMT: ME10031, Bařinka: Racionální návrh ligandů a inhibitorů glutamát karboxypeptidasy II a jejích homologů. 2010-2012.
EMBO: 1978, Bařinka: EMBO Installation Grant. 2010-2015.
AVČR: Fellowship Jana Evangelisty Purkyně. 2010-2014.
FP7 IRG Reintegration Grant: 249220, Bařinka: Design and development of novel reagents, tools, and techniques targeting human glutamate carboxypeptidases II and III. 2010-2014.