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Department of Biochemistry

Publications of PD Dr. Peer Mittl

Pott, M., Tinzl, M., Hayashi, T., Ota, Y., Dunkelmann, D., Mittl, PRE. & Hilvert, D. Noncanonical Heme Ligands Steer Carbene Transfer Reactivity in an Artificial Metalloenzyme*. Angew Chem Int Ed Engl [Epub ahead of print] (2021). PMID: 33880851.

Deluigi, M., Klipp, A., Klenk, C., Merklinger, L., Eberle, SA., Morstein, L., Heine, P., Mittl, PRE., Ernst, P., Kamenecka, TM., He, Y., Vacca, S., Egloff, P., Honegger, A. & Plückthun, A. Complexes of the neurotensin receptor 1 with small-molecule ligands reveal structural determinants of full, partial, and inverse agonism. Sci Adv 7, (2021). PMID: 33571132.

Karakus, U., Sahin, D., Mittl, PRE., Mooij, P., Koopman, G. & Boyman, O. Receptor-gated IL-2 delivery by an anti-human IL-2 antibody activates regulatory T cells in three different species. Sci Transl Med 12, (2020). PMID: 33328333.

Mittl, PR., Ernst, P. & Plückthun, A. Chaperone-assisted structure elucidation with DARPins. Curr Opin Struct Biol 60, 93-100 (2020). PMID: 31918361.

Bunzel, HA., Kries, H., Marchetti, L., Zeymer, C., Mittl, PRE., Mulholland, AJ. & Hilvert, D. Emergence of a Negative Activation Heat Capacity during Evolution of a Designed Enzyme. J. Am. Chem. Soc. 141, 11745-11748 (2019).  PMID: 31282667.

Gall, FM., Hohl, D., Frasson, D., Wermelinger, T., Mittl, PRE., Sievers, M. & Riedl, R. Drug Design Inspired by Nature: Crystallographic Detection of an Auto-Tailored Protease Inhibitor Template. Angew. Chem. Int. Ed. Engl. 58, 4051-4055 (2019).  PMID: 30615822.

Hansen, S., Ernst, P., König, SLB., Reichen, C., Ewald, C., Nettels, D., Mittl, PRE., Schuler, B. & Plückthun, A. Curvature of deignes armadillo repeat proteins allows modular peptide binding. J Struct Biol. 201 108-117 (2018). PMID: 28864298.

Pott M., Hayashi, T., Mori, T., Mittl, P., Green AP & Hilvert, D. A non-canonical proximal heme ligand affords an efficient peroxidase in a globin fold. J. Am. Chem. Soc. 140, 1535-1543 (2018). PMID: 29309143.

Studer, S., Hansen, DA., Pianowski, ZL., Mittl, PRE., Debon, A., Guffy, SL., Der, BS., Kuhlman, B. & Hilvert, D. Evolution of a highly active and enantiospecific metalloenzyme from short peptides. Science 362, 1285-1288 (2018). PMID: 30545884.

Wu,Y., Honegger, A., Batyuk, A., Mittl, P. & Plückthun, A. Structural basis for the selective inhibition of c-Jun N-terminal kinase 1 determined by rigid DARPin-DARPin fusions. J Mol Biol 430, 2128-2138 (2018). PMID: 29126898.

Afroz, T., Hock, EM., Ernst, P., Foglieni, C., Jambeau, M., Gilhespy, LAB., Laferriere, F., Maniecka, Z., Plückthun, A., Mittl, P., Paganetti, P., Allain, FHT. & Polymenidou, M. Functional and dynamic polymerization of the ALS-linked protein TDP-43 antagonizes its pathologic aggregation. Nat Commun 8, 45 (2017). PMID: 28663553.

Hansen, S., Stüber, JC., Ernst, P., Koch, A., Bojar, D., Batyuk, A. & Plückthun, A. Design and applications of a clamp for Green Fluorescent Protein with picomolar affinity. Sci Rep 7, 16292 (2017). PMID: 29176615.

Hansen, S., Kiefer, JD., Madhurantakam, C., Mittl, PRE. & Plückthun, A. Structures of designed armadillo repeat proteins binding to peptides fused to globular domains. Protein Sci. 26, 1942-1952 (2017). PMID: 28691351.

Obexer R, Godina A, Garrabou X, Mittl PR, Baker D, Griffiths AD, Hilvert D. Emergence of a catalytic tetrad during evolution of a highly active artificial aldolase. Nat Chem.9, 50-56 (2017). PMID: 27995916.

Wu, Y., Batyuk, A., Honegger, A., Brandl, F., Mittl, PRE. & Plückthun, A. Rigidly connected multispecific artificial binders with adjustable geometries. Sci Rep 7, 11217 (2017). PMID: 28894181.

Green, AP., Hayashi, T., Mittl, PR. & Hilvert, D. A Chemically Programmed Proximal Ligand Enhances the Catalytic Properties of a Heme Enzyme. J. Am. Chem. Soc.  138, 11344-11352 (2016). PMID: 27500802.

Hansen, S., Tremmel, D., Madhurantakam, C., Reichen, C., Mittl, PR. & Plückthun, A. Structure and energetic contributions of a designed modular peptide-binding protein with picomolar affinity. J. Am. Chem. Soc. 428, 1574-88 (2016). PMID: 26878586.

Reichen, C., Madhurantakam, C., Hansen, S., Grütter, MG., Plückthun, A. & Mittl, PR. Structures of designed armadillo-repeat proteins show propagation of inter-repeat interface effects. Acta Crystallogr D Struct Biol 72, 168-75 (2016). PMID: 26894544.

Schütz, M., Batyuk, A., Klenk, C., Kummer, L., de Picciotto, S., Gülbakan, B., Wu, Y., Newby, GA., Zosel, F., Schöppe, J., Sedlák, E., Mittl, PR., Zenobi, R., Wittrup, KD. & Plückthun, A. Generation of Fluorogen-Activating Designed Ankyrin Repeat Proteins (FADAs) as Versatile Sensor Tools. J. Mol. Biol.  428, 1272-89 (2016). PMID: 26812208.

Weinert, C., Morger, D., Djekic, A., Grütter, MG. & Mittl, PR. Crystal structure of TRIM20 C-terminal coiled-coil/B30.2 fragment: implications for the recognition of higher order oligomers. Sci Rep 5, 10819 (2015). PMID: 26043233.

Reichen, C., Madhurantakam, C., Plückthun, A. & Mittl, PR. Crystal structures of designed armadillo repeat proteins: implications of construct design and crystallization conditions on overall structure. Protein Sci. 23, 1572-83 (2014). PMID: 25132085.

Blomberg, R., Kries, H., Pinkas, DM., Mittl, PR., Grütter, MG., Privett, HK., Mayo, SL. & Hilvert, D. Precision is essential for efficient catalysis in an evolved Kemp eliminase. Nature 503, 418-421 (2013).

Dreier, B., Honegger, A., Hess, C., Nagy-Davidescu, G., Mittl, PR., Grütter, MG., Belousova, N., Mekheeva, G., Krasnykh, V. & Plückthun, A. Development of a generic adenovirus delivery system based on structure-guided design of bispecific trimeric DARPin adapters. PNAS USA 110, E869-877 (2013).

Putty, K., Marcus, SA., Mittl, PR., Bogadi, LE., Hunter, AM., Arur, S., Berg, DE., Sethu, P. & Kalia, A. Robustness of Helicobacter pylori infection conferred by context-variable redundancy among cysteine-rich paralogs. PLoS One 8(3): e59560 (2013). 

Schröder, T., Barandun, J., Flütsch, A., Briand, C., Mittl, PR. & Grütter, MG. Specific inhibition of caspase-3 by a competitive DARPin: molecular mimicry between native and designed inhibitors. Structure 21, 277-289 (2013).

Tschirren,B., Andersson, M., Scherman, K., Westerdahl, H., Mittl, PR. & Raberg, L. Polymorphisms at the innate immune receptor TLR2 are associated with Borrelia infection in a wild rodent population. Proc Biol Sci. 280, 20130364 (2013). 

Kummer, L.,Parizek, P., Rube, P., Millgramm, B., Prinz, A., Mittl, PR., Kaufholz, M., Zimmermann, B., Herberg, FW. & Plückthun, A. Structural and functional analysis of phosphorylation-specific binders of the kinase ERK from designed ankyrin repeat protein libraries. PNAS USA109, E2248-2257 (2012).

Madhurantakam, C., Varadamsetty, G., Grütter, MG., Plückthun, A. & Mittl, PR. Structure-based optimization of designed Armadillo-repeat proteins. Protein Sci. 21, 1015-1028 (2012).

Merz,T., Heck, T. Geueke, B., Mittl, PR., Briand, C., Seebach, D., Kohler, HP. & Grütter, MG. Autoproteolytic and catalytic mechanisms for the beta-aminopeptidase BapA- a member of the Ntn hydrolase family. Structure 20, 1850-1860 (2012). 

Roschitzki-Voser, H., Schröder, T., Lenherr, ED., Frölich, F., Schweizer, A., Donepudi, M., Ganesan, R., Mittl, PR., Baici, A. & Grütter, MG. Human caspases in vitro: expression, purification and kinetic characterization. Protein Expr Purif. 84, 236-246 (2012).

Devi, VS, & Mittl. PR. Monitoring the disulfide bond formation of a cysteine-rich repeat proteine from Helicobacter pylori in the periplasm of escherichia coli. Curr Microbiol. 62, 903-907 (2011).

Ganesan, R., Jelakovic, S., Mittl, PR., Caflisch, A. & Grütter, MG. In silico identification and crystal structure validation of procaspase-3 inhibitors without a P1 aspartic acid moiety. Acta Crystallogr SectF Struct Biol Cryst Commun. 67(Pt8), 842-850 (2011).

Roschitzki, B.,Schauer, S. & Mittl, PR. Recognition of host proteins by Helicobacter cysteine-rich proteine C. Curr Microbiol. 63, 239-249 (2011).

Kindermann, M., Roschitzki-Voser, H., Caglic, D., Repnik, U., Miniejew, C., Mittl, PR., Kosec, & G., Grütter, MG., Turk, B.; Wendt, KU. Selective and sensitive monitoring of caspase-1 activity by a novel bioluminescent activity-based probe. Chem Biol. 17, 999-1007 (2010).

Kramer, MA., Wetzel, SK:, Plückthun, A., Mittl, PR. & Grütter, MG. Structural determinants for improved stability of designed ankyrin repeat proteins with a redesigned c-capping module. J Mol Biol. 404, 381-391 (2010).

Schoep,TD., Fulurija, A., Good, F., Lu, W., Hirnbeck, RP., Schwan, C., Choi, SS., Berg, DE., Mittl, PR., Benghezal, M. & Marshall, BJ. Surface properties of Helicobacter pylori urease complex are essential for persistence. PLoS One. 5 (11): e15042 (2010).

Dumrese, C., Slomianka, L., Ziegler, U., Choi, SS., Kalia, A., Fulurija, A., Lu, W., Berg, DE., Benghezal, M. , Marshall, B. & Mittl, PR. The secreted Heliobacter cysteine-rich protein A causes adherence of human monocytes and differentiation into a macrophage-like phenotype. FEBS Lett. 583, 1637-1643 (2009).

Weinert, C., Grütter, C., Roschitzki-Voser, H., Mittl, PR. & Grütter, M. The crystal structure of human pyrin B30.2 domain: implications for mutations associated with familial mediterranean fever. J Mol Biol. 394, 226-236 (2009).

Merz, T., Wetzel, SK., Firbank, S., Plückthun, A., Grütter, MG .& Mittl, PR. Stabilizing ionic interactions in a full-consensus ankyrin repeat protein. J.Mol. Biol. 376, 231-240 (2008).

Mittl, P.R. & Schneider-Brachert, W. Sel1-like repeat proteins in signal transduction. Cell Signal 19, 20-31 (2007).

Ogura M., Perez, JC., Mittl, PR., Lee, HK., Dailide, G., Tan, S., Ito, Y., Secka, O., Dailidiene, D., Putty, K., Berg, DE. & Kalia, A. Helicobacter pylori evolution: lineage- specific adaptations in homologs of eukaryotic Sel1-like genes. PLoS Comput. Biol. 3, e151 (2007).

Fasan, R., Dias, R.L.., Moehle, K., Zerbe, O., Obrecht, D.,Mittl, P.R.E., Grütter, M.G & Robinson, J.A. Structure-activity studies in a family of beta-hairpin protein epitope mimetic inhibitors of the p53-HDM2 protein-protein interaction. Chembiochem. 7, 515-526 (2006).

Ganesan, R., Mittl, P.R., Jelakovic, S. & Grütter, M.G. Extended substrate recognition in caspase- 3 revealed by high resolution X-ray structure analysis. J. Mol. Biol. 359, 1378-1388 (2006).

Grütter, C., Briand, C., Capitani, G., Mittl, P.R., Papin, S., Tschopp, J. & Grütter, M.G. Structure of the PRYSPRY-domain: implications for autoinflammatory diseases. FEBS Lett. 580, 99-106 (2006).

Mittl, P.R., & Grütter, M.G. Opportunities for structure-based design of protease -directed drugs. Curr. Opin. Struct. Biol. 16, 769-775 (2006).

Lüthy, L., Grütter, M.G. & Mittl, P.R.E. The crystal structure of Helicobacter cysteine rich protein-C reveals a putative peptide-binding site for SEL1-like proteins. Journal of Molecular Biology 340, 829-841 (2004).

Mittl, P.R.E., Lüthy, L., Rheinhard, C. & Joller, H. Detection of high titers of antibody against Helicobacter cysteine-rich proteins A, B, C, and E in Helicobacter pylori-infected individuals. Clinical and Diagnostic Laboratory Immunology 10, 542-545 (2003).

Fritz, G., Mittl, P.R.E., Vasak, M., Grütter, M.G. & Heizmann, C.W. The crystal structure of metal-free human EF-hand protein S100A3 at 1.7 Å resolution. Journal of Biological Chemistry 277, 33092-33098 (2002).

Mittl, P.R.E., Fritz, G., Sargent, D.F., Richmond, T.J., Heizmann C.W. & Grütter, M.G. Metal-free MIRAS phasing: Crystal structure of apo-S100A3. Acta Crystallographica Section D, Biological Crystallography D58, 1255-1261 (2002).

Lüthy, L., Grütter, M.G. & Mittl, P.R.E. The crystal structure of Helicobacter pylori cysteine rich protein B reveals a novel fold for a penicillin binding protein. Journal of Biological Chememistry 277, 10187-10193 (2002).

Flückiger, S., Mittl P.R.E., Scapozza, L., Fijten, H., Folkers, G., Grütter, M.G., Blaser, K. & Crameri R. Comparison of the crystal structures of the human manganese superoxide dismutase and the homologous Aspergillus fumigatus allergen at 2-Å resolution. Journal of Immunology 168, 1267-1272 (2002).

Furet, P., Meyer, T., Mittl, P. & Fretz, H. Identification of cyclin-dependent kinase 1 inhibitors of a new chemical type by structure-based design and database searching. Journal of Computer-Aided Molecular Design 15, 489-495 (2001).

Mittl, P.R.E. & Grütter, M.G. Structural genomics: opportunities and challenges. Current Opinion in Chemical Biology 5, 402-408 (2001).

Tissot, A., Ciatto, C., Mittl, P.R.E., Grütter, M. & Plückthun, A. Viral escape at the molecular level explained by quantitative T-cell receptor/peptide/MHC interactions and crystal structure of a peptide/MHC complex. Journal of Molecular Biology 302, 873-885 (2000).

Mittl, P.R.E., Lüthy, L., Hunziker, P. & Grütter, M.G. The cysteine-rich protein A from Helicobacter pylori is a beta-lactamase. Journal of Biological Chemistry 275, 17693-17699 (2000).

Mittl, P.R.E., Deillon, C., Sargent, D., Liu, N., Klauser, S., Thomas, R.M., Gutte, B. & Grütter, M.G. The retro-GCN4 leucine zipper sequence forms a stable three-dimensional structure. Proceedings of the National Academy of Sciences of the United States of America 97, 2562-2566 (2000).

Blanchard, H., Kodandapani, L., Mittl, P.R.E., Marco, S.D., Krebs, J.F., Wu, J.C., Tomaselli, K.J. & Grütter, M.G. The three-dimensional structure of caspase-8: an initiator enzyme in apoptosis. Structure with Folding & Design 7, 1125-1133 (1999).

Uson, I., Sheldrick, G.M., de La Fortelle, E., Bricogne, G., Di Marco, S., Priestle, J.P., Grütter, M.G. & Mittl, P.R.E. The 1.2 Å crystal structure of hirustasin reveals the intrinsic flexibility of a family of highly disulphide-bridged inhibitors. Structure with Folding & Design 7 55-63 (1999).

Moorthamer, M., Zumstein-Mecker, S., Stephan, C., Mittl, P. & Chaudhuri, B. Identification of a human cDNA encoding a kinase-defective cdk5 isoform. Biochemical & Biophysical Research Communications 253, 305-310 (1998).

Mittl, P.R.E., Chene, P. & Grütter, M.G. Crystallization and structure solution of p53 (residues 326-356) by molecular replacement using an NMR model as template. Acta Crystallographica Section D-Biological Crystallography 54, 86-89 (1998).

Mittl, P. & Grütter, M. Transforming Growth Factor - beta 3 (1, 2). In Haeberli, A. (ed.) Human Protein Data, Wiley-VCH, Weinheim, Vol. 6. (1998).

Mittl, P.R.E., Di Marco, S., Fendrich, G., Pohlig, G., Heim, J., Sommerhoff, C., Fritz, H., Priestle, J.P. & Grütter, M.G. A new structural class of serine protease inhibitors revealed by the structure of the hirustasin-kallikrein complex. Structure with Folding Design 5, 253-264 (1997).

Mittl, P.R.E., Di Marco, S., Krebs, J.F., Bai, X., Karanewsky, D.S., Priestle, J.P., Tomaselli, K.J. & Grütter, M.G. Structure of recombinant human CPP32 in complex with the tetrapeptide acetyl-Asp-Val-Ala-Asp fluoromethyl ketone. Journal of Biological Chemistry272, 6539-6547 (1997).

Chene, P., Mittl, P. & Grütter, M. In vitro structure-function analysis of the beta-strand 326-333 of human p53. Journal of Molecular Biology 273, 873-881 (1997).

Mittl, P.R.E, Priestle, J.P., Cox, D.A., McMaster, G., Cerletti, N. & Grütter, M.G. The crystal structure of TGF-beta 3 and comparison to TGF-beta 2: implications for receptor binding. Protein Science 5, 1261-1271 (1996).

Schonleben-Janas, A., Kirsch, P., Mittl, P.R.E., Schirmer, R.H. & Krauth-Siegel, R.L. Inhibition of human glutathione reductase by 10-arylisoalloxazines: crystalline, kinetic, and electrochemical studies. Journal of Medicinal Chemistry 39, 1549-1554 (1996).

Mittl, P.R.E., Berry, A., Scrutton, N.S., Perham, R.N. & Schulz, G.E. Anatomy of an engineered & NAD-binding site. Protein Science 3, 1504-1514 (1994).

Mittl, P.R.E., Berry, A., Scrutton, N., Perham, R. & Schulz, G. A designed mutant of the enzyme glutathione reductase shortens the crystallisation time by a factor of forty. Acta Crystallographica Section D-Biological Crystallography D50, 228-231(1994).

Mittl, P.R.E. & Schulz, G.E. Structure of glutathione reductase from Escherichia coli at 1.86 A resolution: comparison with the enzyme from human erythrocytes. Protein Science 3 , 799-809 (1994).

Mittl, P.R.E., Berry, A., Scrutton, N.S., Perham, R.N. & Schulz, G.E. Structural differences between wild-type NADP-dependent glutathione reductase from Escherichia coli and a redesigned NAD-dependent mutant. Journal of Molecular Biology 231, 191-195 (1993).

Schulz, G., Dreyer, M., Klein, C., Kreusch, A., Mittl, P., Müller, C., Müller-Dieckmann J, Müller, Y., Proba, K., Schlauderer, G., Spürgin, P., Stehle, T. & Weiss, M. Highly ordered crystals of channel-forming membrane proteins, of nucleoside-monophosphate kinases, of FAD-containing oxidoreductases and of sugar-processing enzymes and their mutants. Journal of Crystal Growth 122 , 385-392 (1992).

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