ZMB Member Robert Huber

ZMB Member
Robert Huber

Next ZMB-Member
portrait photo of ZMB member Robert Huber
© Axel Griesch, MPI for Biochemistry

Prof. Dr. Dr. h.c. mult. Robert Huber FRS

Group

Structure Research

Center of Medical Biotechnology
Room: S03 S02 A45
University of Duisburg-Essen
45141 Essen
Max Planck Institute of Biochemistry
Am Klopferspitz 18
82152 Martinsried

Research Overview

Professional interests

Structure and function of biological macromolecules, in particular those of large complex aggregates.

Systems studied

  • Proteases and their natural and synthetic inhibitors.
  • Metalloenzymes (iron, nickel, molybdenum, copper).
  • Proteins of the immune system (antibodies and antibody receptors).
  • Protein hormones and their receptors.
  • Protein kinases.
  • Proteins of amino acid biosynthesis (PLP containing enzymes).
  • Proteins of cofactor and vitamin biosynthesis.
  • Proteins of energy and electron transport.

Methods development

  • Patterson methods in crystallography.
  • Methods of structure determination of proteins and protein ligand complexes by NMR.
  • Synthesis and use of electron rich metal clusters.
  • Crystal annealing and improvement, methods and instruments.
  • Analysis and evaluation of targets for research and application in pharmacology and crop science.

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Selected Publications

    Journal articles

  • Schillinger, Jasmin; Koci, Michelle; Bravo-Rodriguez, Kenny; Heilmann, Geronimo; Kaschani, Farnusch; Kaiser, Markus; Beuck, Christine; Luecke, Hartmut; Huber, Robert; Hellerschmied-Jelinek, Doris; Burston, Steven G.; Ehrmann, Michael
    High resolution analysis of proteolytic substrate processing
    In: The Journal of Biological Chemistry (JBC) Vol. 300 (2024) Nr. 11, 107812
    Online Full Text: dx.doi.org/ (Open Access)
  • Beaufort, Nathalie; Ingendahl, Linda; Merdanovic, Melisa; Schmidt, Andree; Podlesainski, David; Richter, Tim; Neumann, Thorben; Kuszner, Michael; Vetter, Ingrid R.; Stege, Patricia; Burston, Steven G.; Filipovic, Anto; Ruiz-Blanco, Yasser B.; Bravo Rodriguez, Kenny; Mieres-Perez, Joel; Beuck, Christine; Uebel, Stephan; Zobawa, Monika; Schillinger, Jasmin; Malik, Rainer; Todorov-Völgyi, Katalin; Rey, Juliana; Roberti, Annabell; Hagemeier, Birte; Wefers, Benedikt; Müller, Stephan A.; Wurst, Wolfgang; Sanchez-Garcia, Elsa; Zimmermann, Alexander; Hu, Xiao-Yu; Clausen, Tim; Huber, Robert; Lichtenthaler, Stefan F.; Schmuck, Carsten; Giese, Michael; Kaiser, Markus; Ehrmann, Michael; Dichgans, Martin
    Rational correction of pathogenic conformational defects in HTRA1
    In: Nature Communications Vol. 15 (2024) Nr. 1, 5944
    Online Full Text: dx.doi.org/ (Open Access)
  • Fehr, Lorenz; Sewald, Leonard; Huber, Robert; Kaiser, Markus
    Facile Multicomponent Synthesis of Oxazolidinones from Primary Amines and Cesium (Hydrogen)Carbonate
    In: European Journal of Organic Chemistry Vol. 26 (2023) Nr. 27, e202300135
    Online Full Text: dx.doi.org/ (Open Access)
  • Wolf, Christine; Fischer, Hannah; Kühl, Jörn-Sven; Koss, Sarah; Jamra, Rami Abou; Starke, Sven; Schultz, Jurek; Ehl, Stephan; Neumann, Katrin; Schuetz, Catharina; Huber, Robert; Hornung, Veit; Lee-Kirsch, Min Ae
    Hemophagocytic lymphohistiocytosis : Like hyperinflammation due to a de novo mutation in DPP9
    In: The Journal of Allergy and Clinical Immunology Vol. 152 (2023) Nr. 5, pp. 1336 - 1344.e5
    Online Full Text: dx.doi.org/
  • Carvalho, Luís A. R.; Ross, Breyan; Fehr, Lorenz; Bolgi, Oguz; Wöhrle, Svenja; Lum, Kenneth M.; Podlesainski, David; Vieira, Andreia C.; Kiefersauer, Reiner; Félix, Rita; Rodrigues, Tiago; Lucas, Susana D.; Groß, Olaf; Geiss‐Friedlander, Ruth; Cravatt, Benjamin F.; Huber, Robert; Kaiser, Markus; Moreira, Rui
    Chemoproteomics‐Enabled Identification of 4‐Oxo‐β‐Lactams as Inhibitors of Dipeptidyl Peptidases 8 and 9
    In: Angewandte Chemie International Edition Vol. 61 (2022) Nr. 47, e202210498
    Online Full Text: dx.doi.org/ (Open Access)
  • Bolgi, Oguz; Silva-Garcia, Maria; Ross, Breyan; Pilla, Esther; Kari, Vijayalakshmi; Killisch, Markus; Spitzner, Melanie; Stark, Nadine; Lenz, Christof; Weiss, Konstantin; Donzelli, Laura; Gorrell, Mark D.; Grade, Marian; Riemer, Jan; Urlaub, Henning; Dobbelstein, Matthias; Huber, Robert; Geiss-Friedlander, Ruth
    Dipeptidyl peptidase 9 triggers BRCA2 degradation and promotes DNA damage repair
    In: EMBO Reports Vol. 23 (2022) Nr. 10, e54136
    Online Full Text: dx.doi.org/ (Open Access)
  • Ross, Breyan; Krapp, Stephan; Geiss-Friedlander, Ruth; Littmann, Walter; Huber, Robert; Kiefersauer, Reiner
    Aerosol-based ligand soaking of reservoir-free protein crystals
    In: Journal of Applied Crystallography Vol. 54 (2021) Nr. 3, pp. 895 - 902
    Online Full Text: dx.doi.org/ (Open Access)
  • Lee, Jung-Hoon; Bollschweiler, Daniel; Schäfer, Tillman; Huber, Robert
    Structural basis for the regulation of nucleosome recognition and HDAC activity by histone deacetylase assemblies
    In: Science Advances Vol. 7 (2021) Nr. 2, pp. eabd4413
    Online Full Text: dx.doi.org/ (Open Access)
  • Klatt, Felix; Leitner, Alexander; Kim, Iana V.; Ho-Xuan, Hung; Schneider, Elisabeth V.; Langhammer, Franziska; Weinmann, Robin; Müller, Melanie R.; Huber, Robert; Meister, Gunter; Kuhn, Claus-D.
    A precisely positioned MED12 activation helix stimulates CDK8 kinase activity
    In: Proceedings of the National Academy of Sciences of the United States of America (PNAS) Vol. 117 (2020) Nr. 6, pp. 2894 - 2905
    Online Full Text: dx.doi.org/ Online Full Text (Open Access)
  • Merdanovic, Melisa; Burston, Steven G.; Schmitz, Anna Laura; Köcher, Steffen; Knapp, Stefan; Clausen, Tim; Kaiser, Markus; Huber, Robert; Ehrmann, Michael
    Activation by substoichiometric inhibition
    In: Proceedings of the National Academy of Sciences of the United States of America (PNAS) Vol. 117 (2020) Nr. 3, pp. 1414 - 1418
    Online Full Text: dx.doi.org/ Online Full Text (Open Access)
  • Garcia-Guerrero, Maria C.; Garcia-Pardo, Javier; Berenguer, Esther; Fernandez-Alvarez, Roberto; Barfi, Gifty B.; Lyons, Peter J.; Aviles, Francesc X.; Huber, Robert; Lorenzo, Julia; Reverter, David
    Crystal structure and mechanism of human carboxypeptidase O : Insights into its specific activity for acidic residues
    In: Proceedings of the National Academy of Sciences of the United States of America (PNAS) Vol. 115 (2018) Nr. 17, pp. E3932 - E3939
    Online Full Text: dx.doi.org/ (Open Access)
  • Ross, Breyan; Krapp, Stephan; Augustin, Martin; Kierfersauer, Reiner; Arciniega, Marcelino; Geiss-Friedlander, Ruth; Huber, Robert
    Structures and mechanism of dipeptidyl peptidases 8 and 9, important players in cellular homeostasis and cancer
    In: Proceedings of the National Academy of Sciences of the United States of America (PNAS) Vol. 115 (2018) Nr. 7, pp. E1437 - E1445
    Online Full Text: dx.doi.org/ (Open Access)
  • Dahms, Sven O.; Arciniega, Marcelino; Steinmetzer, Torsten; Huber, Robert; Than, Manuel E.
    Structure of the unliganded form of the proprotein convertase furin suggests activation by a substrate-induced mechanism
    In: Proceedings of the National Academy of Sciences of the United States of America (PNAS) Vol. 113 (2016) Nr. 40, pp. 11196 - 11201
    Online Full Text: dx.doi.org/ (Open Access)
  • Hierold, Judith; Baek, Sohee; Rieger, Rene; Lim, Tae-Guy; Zakpur, Saman; Arciniega, Marcelino; Lee, Kiwon; Huber, Robert; Tietze, Lutz Friedjan
    Design, Synthesis, and Biological Evaluation of Quercetagetin Analogues as JNK1 Inhibitors
    In: Chemistry - A European Journal Vol. 21 (2015) Nr. 47, pp. 16887 - 16894
    Online Full Text: dx.doi.org/
  • Park, Gaeun; Baek, Sohee; Kim, Jong-Eun; Lim, Tae-gyu; Lee, Charles C.; Yang, Hee; Kang, Young-Gyu; Park, Jun Seong; Augustin, Martin; Mrosek, Michael; Lee, Chang Yong; Dong, Zigang; Huber, Robert; Lee, Ki Won
    Flt3 is a target of coumestrol in protecting against UVB-induced skin photoaging
    In: Biochemical Pharmacology Vol. 98 (2015) Nr. 3, pp. 473 - 483
    Online Full Text: dx.doi.org/
  • Beaufort, Nathalie; Scharrer, Eva; Kremmer, Elisabeth; Lux, Vanda; Ehrmann, Michael; Huber, Robert; Houlden, Henry H.; Werring, David John; Haffner, Christof; Dichgans, Martin
    Cerebral small vessel disease-related protease HtrA1 processes latent TGF-β binding protein 1 and facilitates TGF-β signaling
    In: Proceedings of the National Academy of Sciences of the United States of America (PNAS) Vol. 111 (2014) Nr. 46, pp. 16496 - 16501
    Online Full Text: dx.doi.org/
  • Arciniega, M.; Beck, P.; Lange, O. F.; Groll, M.; Huber, Robert
    Differential global structural changes in the core particle of yeast and mouse proteasome induced by ligand binding
    In: Proceedings of the National Academy of Sciences of the United States of America (PNAS) Vol. 111 (2014) Nr. 26, pp. 9479 - 9484
    Online Full Text: dx.doi.org/
  • Kiefersauer, Reiner; Grandl, Brigitte; Krapp, S.; Huber, Robert
    IR laser-induced protein crystal transformation
    In: Acta Crystallographica Section D: Biological Crystallography Vol. D70 (2014) Nr. 5, pp. 1224 - 1232
    Online Full Text: dx.doi.org/ (Open Access)
  • Lesca, E.; Lammens, A.; Huber, Robert; Augustin, M.
    Structural analysis of the human fibroblast growth factor receptor 4 kinase
    In: Journal of Molecular Biology (JMB) Vol. 426 (2014) Nr. 22, pp. 3744 - 3756
    Online Full Text: dx.doi.org/
  • Baek, Sohee; Kang, Nam Joo; Popowicz, Grzegorz M.; Arciniega, Marcelino; Jung, Sung Keun; Byun, Sanguine; Song, Nu Ry; Heo, Yong-Seok; Kim, Bo Yeon; Lee, Hyong Joo; Holak, Tad A.; Augustin, Martin; Bode, Ann M.; Huber, Robert; Dong, Zigang; Lee, Ki Won
    Structural and Functional Analysis of the Natural JNK1 Inhibitor Quercetagetin
    In: Journal of Molecular Biology (JMB) Vol. 425 (2013) Nr. 2, pp. 411 - 423
    Online Full Text: dx.doi.org/ Online Full Text (Open Access)
  • Schneider, Elisabeth V.; Böttcher, Jark; Huber, Robert; Maskos, Klaus; Neumann, Lars
    Structure-kinetic relationship study of CDK8/CycC specific compounds
    In: Proceedings of the National Academy of Sciences of the United States of America (PNAS) Vol. 110 (2013) Nr. 20, pp. 8081 - 8086
    Online Full Text: dx.doi.org/
  • Huber, Robert
    “How I Chose Research on Proteases or, More Correctly, How it Chose Me”
    In: Angewandte Chemie International Edition Vol. 52 (2013) Nr. 1, pp. 68 - 73
    Online Full Text: dx.doi.org/
  • Weski, Juliane; Meltzer, Michael; Spaan, Lina; Mönig, Timon; Oeljeklaus, Julian; Hauske, Patrick; Vouilleme, Lars; Volkmer, Rudolf; Boisguerin, Prisca; Boyd, Dana; Huber, Robert; Kaiser, Markus; Ehrmann, Michael
    Chemical Biology Approaches Reveal Conserved Features of a C-Terminal Processing PDZ Protease
    In: ChemBioChem Vol. 13 (2012) Nr. 3, pp. 402 - 408
    Online Full Text: dx.doi.org/
  • Tennstaedt, Annette; Pöpsel, Simon; Trübestein, Linda; Hauske, Patrick; Brockmann, Anke; Schmidt, Nina; Irle, Inga; Sacca, Barbara; Niemeyer, Christof M.; Brandt, Roland; Ksiezak-Reding, Hanna; Tirniceriu, Anca Laura; Egensperger, Rupert; Baldi, Alfonso; Dehmelt, Leif; Kaiser, Markus; Huber, Robert; Clausen, Tim; Ehrmann, Michael
    Human high temperature requirement serine protease A1 (HTRA1) degrades tau protein aggregates
    In: The Journal of Biological Chemistry (JBC) Vol. 287 (2012) Nr. 25, pp. 20931 - 20941
    Online Full Text: dx.doi.org/
  • Gallastegui, Nerea; Beck, Philipp; Arciniega, Marcelino; Huber, Robert; Hillebrand, Stefan; Groll, Michael
    Hydroxyureas as noncovalent proteasome inhibitors
    In: Angewandte Chemie International Edition Vol. 51 (2012) Nr. 1, pp. 247 - 249
    Online Full Text: dx.doi.org/
  • Baek, Sohee; Kutchukian, Peter S.; Verdine, Gregory L.; Huber, Robert; Holak, Tad A.; Lee, Ki Won; Popowicz, Grzegorz M.
    Structure of the stapled p53 peptide bound to Mdm2
    In: Journal of the American Chemical Society: JACS Vol. 134 (2012) Nr. 1, pp. 103 - 106
    Online Full Text: dx.doi.org/
  • Gallastegui, Nerea; Stein, Martin; Schmidt, Boris; Kloetzel, Peter-Michael; Huber, Robert; Groll, Michael; Gräwert, Melissa Ann
    Elucidation of the α-keto-aldehyde binding mechanism : A lead structure motif for proteasome inhibition
    In: Angewandte Chemie International Edition Vol. 50 (2011) Nr. 2, pp. 542 - 544
    Online Full Text: dx.doi.org/
  • Clausen, Tim; Kaiser, Markus; Huber, Robert; Ehrmann, Michael
    HTRA proteases : regulated proteolysis in protein quality control
    In: Nature Reviews Molecular Cell Biology Vol. 12 (2011) Nr. 3, pp. 152 - 162
    Online Full Text: dx.doi.org/
  • Sitar, Tomasz; Gallinger, Julia; Ducka, Anna M.; Ikonen, Teemu P.; Wohlhoefler, Michael; Schmoller, Kurt M.; Bausch, Andreas R.; Joel, Peteranne; Trybus, Kathleen M.; Noegel, Angelika A.; Schleicher, Michael; Huber, Robert; Holak, Tad A.
    Molecular architecture of the Spire-actin nucleus and its implication for actin filament assembly
    In: Proceedings of the National Academy of Sciences of the United States of America (PNAS) Vol. 108 (2011) Nr. 49, pp. 19575 - 19580
    Online Full Text: dx.doi.org/ Online Full Text (Open Access)
  • Merdanovic, Melisa; Clausen, Tim; Kaiser, Markus; Huber, Robert; Ehrmann, Michael
    Protein quality control in the bacterial periplasm
    In: Annual Review of Microbiology Vol. 65 (2011) pp. 149 - 168
    Online Full Text: dx.doi.org/
  • Schneider, Elisabeth V.; Böttcher, Jark; Blaesse, Michael; Neumann, Lars; Huber, Robert; Maskos, Klaus
    The structure of CDK8/CycC implicates specificity in the CDK/cyclin family and reveals interaction with a deep pocket binder
    In: Journal of Molecular Biology (JMB) Vol. 412 (2011) Nr. 2, pp. 251 - 266
    Online Full Text: dx.doi.org/
  • Clerc, Jérôme; Schellenberg, Barbara; Groll, Michael; Bachmann, André S.; Huber, Robert; Dudler, Robert; Kaiser, Markus
    Convergent synthesis and biological evaluation of syringolin a and derivatives as eukaryotic 20S proteasome inhibitors
    In: European Journal of Organic Chemistry (2010) Nr. 21, pp. 3991 - 4003
    Online Full Text: dx.doi.org/
  • Hasenbein, Sonja; Meltzer, Michael; Hauske, Patrick; Kaiser, Markus; Huber, Robert; Clausen, Tim; Ehrmann, Michael
    Conversion of a regulatory into a degradative protease
    In: Journal of Molecular Biology (JMB) Vol. 397 (2010) Nr. 4, pp. 957 - 966
    Online Full Text: dx.doi.org/
  • Merdanovic, Melisa; Mamant, Nicolette; Meltzer, Michael; Poepsel, Simon; Auckenthaler, Alexandra; Melgaard, Rie; Hauske, Patrick; Nagel-Steger, Luitgard; Clarke, Anthony R.; Kaiser, Markus; Huber, Robert; Ehrmann, Michael
    Determinants of structural and functional plasticity of a widely conserved protease chaperone complex
    In: Nature Structural & Molecular Biology Vol. 17 (2010) Nr. 7, pp. 837 - 843
    Online Full Text: dx.doi.org/
  • Krojer, Tobias; Sawa, Justyna; Huber, Robert; Clausen, Tim
    HtrA proteases have a conserved activation mechanism that can be triggered by distinct molecular cues
    In: Nature Structural & Molecular Biology Vol. 17 (2010) Nr. 7, pp. 844 - 852
    Online Full Text: dx.doi.org/
  • Ducka, Anna M.; Joel, Peteranne; Popowicz, Grzegorz M.; Trybus, Kathleen M.; Schleicher, Michael; Noegel, Angelika A.; Huber, Robert; Holak, Tad A.; Sitar, Tomasz
    Structures of actin-bound Wiskott-Aldrich syndrome protein homology 2 (WH2) domains of Spire and the implication for filament nucleation
    In: Proceedings of the National Academy of Sciences of the United States of America (PNAS) Vol. 107 (2010) Nr. 26, pp. 11757 - 11762
    Online Full Text: dx.doi.org/ Online Full Text (Open Access)
  • Ottmann, Christian; Rose, Rolf; Huttenlocher, Franziska; Cedzich, Anna; Hauske, Patrick; Kaiser, Markus; Huber, Robert; Schaller, Andreas
    Structural basis for Ca2+-independence and activation by homodimerization of tomato subtilase 3
    In: Proceedings of the National Academy of Sciences of the United States of America (PNAS) Vol. 106 (2009) Nr. 40, pp. 17223 - 17228
    Online Full Text: dx.doi.org/
  • Meltzer, Michael; Hasenbein, Sonja; Mamant, Nicolette; Merdanovic, Melisa; Poepsel, Simon; Hauske, Patrick; Kaiser, Markus; Huber, Robert; Krojer, Tobias; Clausen, Tim; Ehrmann, Michael
    Structure, function and regulation of the conserved serine proteases DegP and DegS of Escherichia coli
    In: Research in Microbiology Vol. 160 (2009) Nr. 9, pp. 660 - 666
    Online Full Text: dx.doi.org/
  • Clerc, Jérôme; Groll, Michael; Illich, Damir J.; Bachmann, André S.; Huber, Robert; Schellenberg, Barbara; Dudler, Robert; Kaiser, Markus
    Synthetic and structural studies on Syringolin A and B reveal critical determinants for selectivity and potency of proteasome inhibition
    In: Proceedings of the National Academy of Sciences of the United States of America (PNAS) Vol. 106 (2009) Nr. 16, pp. 6507 - 6512
    Online Full Text
  • Clerc, Jérôme; Florea, Bogdan I.; Kraus, Marianne; Groll, Michael; Huber, Robert; Bachmann, André S.; Dudler, Robert; Driessen, Christoph; Overkleeft, Herman S.; Kaiser, Markus
    Syringolin A selectively labels the 20S proteasome in murine EL4 and wildtype and bortezomib adapted leukemic cell lines
    In: ChemBioChem Vol. 10 (2009) Nr. 16, pp. 2638 - 2643
    Online Full Text: dx.doi.org/ Online Full Text
  • Groll, Michael; Schellenberg, Barbara; Bachmann, André S.; Archer, Crystal R.; Huber, Robert; Powell, Tracy K.; Lindow, Steven; Kaiser, Markus; Dudler, Robert
    A plant pathogen virulence factor inhibits the eukaryotic proteasome by a novel mechanism
    In: Nature Vol. 452 (2008) pp. 755 - 758
    Online Full Text
  • Krojer, Tobias; Pangerl, Karen; Kurt, Juliane; Sawa, Justyna; Stingl, Christoph; Mechtler, Karl; Huber, Robert; Ehrmann, Michael; Clausen, Tim
    Interplay of PDZ and protease domain of DegP ensures efficient elimination of misfolded proteins
    In: Proceedings of the National Academy of Sciences of the United States of America (PNAS) Vol. 22 (2008) pp. 7702 - 7707
    Online Full Text
  • Kaiser, Markus; Groll, Michael; Siciliano, Carlo; Assfalg-Machleidt, Irmgard; Weyher, Elisabeth; Kohno, Jun; Milbradt, Alexander G.; Renner, Christian; Huber, Robert; Moroder, Luis
    Binding mode of TMC-95A analogues to eukaryotic 20S proteasome
    In: ChemBioChem Vol. 5 (2004) Nr. 9, pp. 1256 - 1266
    Online Full Text: dx.doi.org/
  • Kim, Jeong-Sun; Groll, Michael; Musiol, Hans-Jürgen; Behrendt, Raymond; Kaiser, Markus; Moroder, Luis; Huber, Robert; Brandstetter, Hans
    Navigation inside a protease: Substrate selection and product exit in the tricorn protease from Thermoplasma acidophilum
    In: Journal of Molecular Biology (JMB) Vol. 324 (2002) Nr. 5, pp. 1041 - 1050
    Online Full Text: dx.doi.org/
  • Kaiser, Markus; Groll, Michael; Renner, Christian; Huber, Robert; Moroder, Luis
    The Core Structure of TMC-95A Is a Promising Lead for Reversible Proteasome Inhibition
    In: Angewandte Chemie International Edition Vol. 41 (2002) Nr. 5, pp. 780 - 783
    Online Full Text: dx.doi.org/
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