Biochemie II

Research

In the focus of our research are enzymes, which are elaborate proteins that catalyse cellular reactions with high specificity and efficiency.

Model system

Our preferred model system is the (βα)₈-barrel family of enzymes, which is the most frequently encountered protein fold. (βα)₈-barrel enzymes catalyse a large variety of mechanistically diverse reactions. The fold of the canonical (βα)₈-barrel consists of a central barrel of eight parallel β-strands, which are surrounded by eight external α-helices. Connecting loops are located at both the N-terminal (α-β loops) and the C-terminal (β-α loops) face of the barrel. Due to the spatial separation of structural elements that are important for stability and catalytic activity, (βα)₈-barrels provide an ideal scaffold for the study of enzyme evolution and the design of new enzymatic activities.

Projects

We are using rational design and directed evolution to engineer the stability and catalytic activity of enzymes, experimentally reconstruct the natural evolution of enzymes, assign functions to uncharacterised enzymes, and characterize allosteric interactions within multi-enzyme complexes. To this end, we apply a broad range of experimental and computational methods.

Team-Leaders

Chair:
Prof. Dr. Reinhard Sterner

Empty80x80

Prof. Dr. Rainer Merkl

Empty80x80

Dr. Patrick Babinger

Alumni

Dr. Silke Beissmann-Driemeier	Jan 1998 - Jan 2001
Vera Röhlich	Juli 2000 - Juni 2001
Dr. Martina Henn-Sax	Sept 1998 - Dez 2001
Dr. Andreas Ivens	Jan 2000 - Juni 2002
Dr. Stefan Hettwer	Apr 1998 - Sept 2002
Dr. Satoshi Akanuma	Juli 2001 - Feb 2003
Dr. Birte Höcker	Nov 1998 - Juni 2003
Dr. Manal Bosnali	Okt 2002 - März 2004
Natalie Heuer	Okt 2002 - März 2004
Simona Jansen	Juli 2000 - April 2004
Iris Lambeck	Dez 2003 - Dez 2004
Dr. Catharina Dönges	März 2000 - Jan 2005
Susanne Marquardt	April 2004 - März 2005
Birgit Schwarz	Dez 2003 - April 2005
Dr. Michaela Häger	Feb 2001 - Juni 2005
Dr. Karin Babinger	Juni 2005 - Okt 2005
Dr. Sonja Leopoldseder	2001 - Jan 2006
Christian Bolz	Jan 2006 - Nov 2006
Maximilian Plank	Juni 2006 - Aug 2007
Lorella Ungar	Jan 2004 - Aug 2007
Matthias Zwick	Sep 2006 - Dez 2007
Dr. Markus Richter	Mai 2004 - Aug 2008
Dr. Jörg Claren	Nov 2004 - Dez 2008
Ulrike Eßlinger	Juni 2008 - Mai 2009
Daniel Roderer	Sep 2008 - Aug 2009
Bettina Sommer	Feb 2009 - Nov 2009
Dr. Felix List	Nov 2004 - März 2010
Dr. Alexander Ehrmann	Okt 2005 - Aug 2010
Dr. Tobias Seitz	April 2006 - Sept 2010
Nadine Borst	Jan 2010 - Sept 2010
Dr. Thomas Schwab	Jan 2006 - Dez 2010
Dr. Susanne Dietrich	Okt 2005 - Dez 2010
Dr. Harald Guldan	Feb 2007 - Juni 2011
Dr. Marco Bocola	Okt 2006 - Juli 2011
Dr. Hermann Zellner	April 2007 - Okt 2011
Barbara Beer	Mai 2011 - Mai 2012
Dr. Daniel Schneider	Dez 2006 - Mai 2012
Dr. Linn Carstensen	Okt 2008 - Juni 2012
Veronika Schmid	Jan 2012 - Sept 2012
Bastian Groitl	Jan 2012 - Sept 2012
Dr. Monika Meier	Feb 2008 - Jan 2013
Dr. Dietmar Birzer	März 2009 - Aug 2013
Dr. Josef Sperl	Aug 2009 - Aug 2013
Dr. David Peterhoff	Aug 2009 - Okt 2013
Dr. Bernd Reisinger	Aug 2009 - Juli 2014
Dr. Florian Busch	Jan 2010 - Aug 2015
Dr. Alexandra Holinski	Nov 2011 - Apr 2017
Dr. Patrick Löffler	Dez 2012 - Mai 2017
Dr. Wolfgang Kaiser	Jan 2013 - Sept 2017

Publications

The following list summarizes all contributions of the scientific employees

2018 - 2017

Schlee, S., Klein, T., Schumacher, M., Nazet J., Merkl, R., Steinhoff, H.J. & Sterner, R. (2018). Relationship of catalysis and active site loop dynamics in the (βα)₈-barrel enzyme indole-3-glycerol phyosphate synthase. Biochemistry doi: 10.1021/acs.biochem.8b00167 [Epub ahead of print].

Rohweder, B., Semmelmann, F., Endres, C. & Sterner, R. (2018). Standardized cloning vectors for protein production and generation of large gene libraries in Escherichia coli. Biotechniques 64, 24-26.

Antranikian, G., Suleiman, M., Schäfers, C., Adams, MWW., Bartolucci, S., Blamey, JM., Birkeland, NK., Bonch-Osmolovskaya, E., da Costa, MS., Cowan, D., Danson, M., Forterre, P., Kelly, R., Ishino, Y., Littlechild, J., Moracci, M., Noll, K., Oshima, T., Robb, F., Rossi, M., Santos, H., Schönheit, P., Sterner, R., Thauer, R., Thomm, M., Wiegel, J., Stetter, KO. (2017). Diversity of bacteria and archaea from two shallow marine hydrothermal vents from Vulcano Island. Extremophiles 4, 733-742.

Plach, M. G., Semmelmann, F., Busch, F., Busch, M., Heizinger, L., Wysocki, V. H., Merkl, R. & Sterner, R. (2017). Evolutionary diversification of protein-protein interactions by interface add-ons. Proc. Natl. Acad. Sci. USA 114, E8333-E8842

Kandlinger, F., Plach, M. G., & Merkl, R. (2017). AGeNNT: annotation of enzyme families by means of refined neighborhood networks. BMC Bioinformatics 18, 274

Simeth, N. A., Kneuttinger, A. C., Sterner, R. & König, B. (2017). Photochromic coenzyme Q derivatives: switching redox potentials with light Chem. Sci. 8, 6474-83.

Löffler, P., Schmitz, S., Hupfeld, E., Sterner, R. & Merkl, R. (2017). Rosetta: MSF: a modular framework for multi-state computational protein design. PLoS Comput Biol 13, e1005600.

Holinski, A., Heyn, K., Merkl, R. & Sterner, R. (2017). Combining ancestral sequence reconstruction with protein design to identify an interface hotspot in a key metabolic enzyme complex. Proteins 85, 312-321.

Veprinskiy, V., Heizinger, L., Plach, M. G. &. Merkl, R. (2017). Assessing in silico the recruitment and functional spectrum of bacterial enzymes from secondary metabolism. BCM Evol. Biol. 17, 36..

2016 - 2015

Ruther, J., Hagström, A.K., Brandstetter, B., Hofferbert, J., Bruckmann, A., Semmelmann, F., Fink, M., Lowack, H., Laberer, S., Niehuis, O., Deutzmann, R., Löfstedt, C. & Sterner, R. (2016). Epimerisation of chiral hydroxylactones by short-chain dehydrogenases / reductases accounts for sex pheromone evolution in Nasonia. Sci. Rep., 6:34697.

Linde, M., Peterhoff, D., Sterner, R. & Babinger, P. (2016). Identification and characterization of heptaprenylglyceryl phosphate processing enzymes in Bacillus subtilis. J. Biol. Chem 291,14861-70.

Busch, F., Rajendran, C., Heyn, K., Schlee, S., Merkl, R. & Sterner, R. (2016). Ancestral tryptophan synthase reveals functional sophistication of primordial enzyme complexes. Cell Chem. Biol. 23, 709-715.

Plach, M. G., Reisinger, B., Sterner, R. & Merkl, R. (2016). Long-term persistence of bi-functionality contributes to the robustness of microbial life through exaptation. PLoS Genet. 12, e1005836.

Plach, M. G., Löffler, P., Merkl, R. & Sterner, R. (2015). Conversion of anthranilate synthase into isocorismate synthase: implications for the evolution of chorismate-utilizing enzymes. Angew. Chem. Int. Ed. Engl. 54, 11270-11274.

Ece S., Evran, S., Janda, J. O. Merkl, R. & Sterner, R. (2015). Improving thermal and detergent stability of Bacillus stearothermophilus neopullulanase by rational enzyme design. Protein Eng Des Sel 28, 147-151.

Woriedh, M., Merkl, R. & Dresselhaus, T. (2015). Maize EMBRYO SAC family peptides interact differentially with pollen tubes and fungal cells. J .Exp. Bot. 66, 5205-5216.

Filarsky, M., Zillner, K., Araya, I., Villar-Garea, A., Merkl, R., Längst, G. & Németh, A. (2015). The extended AT-hook is a novel RNA binding motif. RNA Biol. 12, 864-876.

Schneider, D., Kaiser, W., Stutz, C., Holinski, A., Mayans, O. & Babinger, P. (2015). YbiB from Escherichia coli, the defining member of the novel TrpD2 family of prokaryotic DNA-binding proteins. J .Biol.Chem. 290, 19527-19539.

2014 - 2013

Diermeier, S., Kolovos, P., Heizinger, L., Schwartz, U., Georgomanolis, T., Zirkel, A., Wedemann, G., Grosveld, F., Knoch, T. A., Merkl, R., Cook, P. R., Längst, G. & Papantonis, A. (2014). TNAα signalling primes chromatin for NF-_kB binding and induces rapid and widespread nucleosome repositioning. Genome Biol. 15, 536.

Hauptmann, J., Kater, L., Löffler, P., Merkl, R. & Meister, G. (2014). Generation of catalytic human Ago4 identifies structural elements important for RNA cleavage. RNA 20, 1532-1538.

Blaul, B., Steinbauer, R., Merkl. P., Merkl, R., Tschochner, H. & Ruther, J. (2014). Oleic acid is a precursor of linoleic acid and the male sex pheromone in Nasonia vitripennis. Insect. Biochem. Mol. Biol. 51, 33-40.

Janda, J. O., Popal, A., Bauer, J., Busch, M., Klocke, M., Spitzer, W., Keller, J. & Merkl, R. (2014). H2rs: deducing evolutionary and functionally important residue positions by means of an entropy and similarity based analysis of multiple sequence alignments. BMC Bioinformatics 15, 118.

Loedige, I., Stotz, M., Qamar, S., Kramer, K., Hennig, J., Schubert, T., Löffler, P., Merkl, R., Urlaub, H. & Meister, G. (2014). The NHL domain of BRAT is an RNA-binding domain that directly contacts the hunchback mRNA for regulation. Genes Dev. 28, 749-764.

Busch, F., Rajendran, C., Mayans, O. Löffler, P., Merkl, R. & Sterner, R. (2014). TrpB2 Enzymes are O-Phospho-L-serine Dependent Tryptophan. Biochemistry 53, 6078-6083.

Peterhoff, D., Beer, B., Rajendran, C., Kumpula, E.P., Kapetaniou, E., Guldan, H., Wierenga, R.K., Sterner, R. & Babinger, P. (2014). A comprehensive analysis of the geranylgeranylglyceryl phosphate synthase enzyme family identifies novel members and reveals mechanisms of substrate specificity and quaternary structure organization. Mol. Microbiol. 92, 885-899.

Sommer, B., Waege, I., Pöllmann, D., Seitz, T., Thomm, M., Sterner, R. & Hausner, W. (2014). Activation of a chimeric Rpb5/RpoH subunit using library selection. PLoS One 9, e87485.

Reisinger, B., Kuzmanovic, N., Löffler, P., Merkl, R., König, B. & Sterner, R. (2014). Expoiting protein symmetry to design light-controllable enzyme inhibitors. Angew. Chem. Int. Ed. 53, 595-598.

Reisinger, B., Sperl, J., Holinski, A., Schmid, V., Rajendran, C., Carstensen, L., Schlee, S., Blanquart, S., Merkl, R. & Sterner, R. (2014). Evidence for the existence of elaborate enzyme complexes in the paleoarchean era. J. Am. Chem. Soc. 136, 122-129.

Janda, J. O., Meier, A. & Merkl, R. (2013). CLIPS-4D: a classifier that distinguishes structurally and functionally important residue-positions based on sequence and 3D data. Bioinformatics 29, 3029-3035.

Sperl, J. M., Rohweder, B., Rajendran, C. & Sterner, R. (2013). Establishing catalytic activity on an artificial (βα)₈-barrel protein designed from identical half-barrels. FEBS Lett.. 587, 2798-2805.

Meier, M.M., Rajendran, C., Malisi, C., Fox, N.G., Xu, C., Schlee, S., Barondeau, D.P. Hoecker, B., Sterner, R. & Raushel, F.M. (2013). Molecular engineering of organophosphate hydrolysis activity from a weak promiscuous lactonase template. J. Am. Chem. Soc. 135, 11670-11677.

Hauptmann, J., Dueck, A., Harlander, S., Pfaff, J., Merkl, R. & Meister, G. (2013). Turning catalytically inactive human Argonaute proteins into active slicer enzymes. Nat. Struct. Mol. Biol. 20, 814-817.

Schlee, S., Dietrich, S., Kurcon, T., Delaney, P., Goodey, N.M. & Sterner, R. (2013). Kinetic mechanism of indole-3-glycerol phosphate synthase. Biochemistry 52, 132-142.

2012 - 2011

List, F., Vega, M. C., Razeto, A., Haeger, M. C., Sterner, R. & Wilmanns, M. (2012). Catalysis uncoupling in a glutamine amidotransferase bienzyme by unblocking the glutaminase active site. Chem. Biol. 19, 1589-1599.

Reisinger, B., Bocola, M., List, F., Claren, J., Rajendran, C. & Sterner, R. (2012). A sugar isomerization reaction established on various (βα)₈ -barrel scaffolds is based on substrate-assisted catalysis. Protein Eng. Des. Sel. 11, 751-760.

Carstensen, L., Sperl, J. M., Bocola, M., List, F., Schmid, F. X. & Sterner, R. (2012). Conservation of the folding mechanism between designed primordial (βα)₈-barrel proteins and their modern descendant. J. Am. Chem. Soc. 134, 12786-12791.

Dietrich, S., Borst, N., Schlee, S., Schneider, D., Janda, J. O., Sterner, R. & Merkl, R. (2012). Experimental assessment of the importance of amino acid positions identified by an entropy-based correlation analysis of multiple sequence alignments. Biochemistry 51, 5633-5641.

Peterhoff, D., Zellner, H., Gudan, H., Merkl, R., Sterner, R. & Babinger, P. (2012). Dimerization determines substrate specificity of a bacterial prenyltransferase. ChemBioChem 13, 1297-1303.

Evran, S., Telefoncu, A. & Sterner, R. (2012). Directed evolution of (βα)₈-barrel enzymes: establishing phosphoribosylanthranilate isomerisation activity on the scaffold of the tryptophan synthase α-subunit. Protein Eng. Des. Sel. 25, 285-293.

Craig, D. B., Schwab, T. & Sterner, R. (2012). Random mutagenesis suggests that sequence errors are not a major cause of variation in the activity of individual

molecules of β-galactosidase. Biochem. Cell Biol. 90, 540-547.

Carstensen, L., Zoldák, G., Schmid, F. X. & Sterner, R. (2012). Folding mechanism of an extremely thermostable (βα)₈-barrel enzyme: a high kinetic barrier protects the protein from denaturation. Biochemistry 51, 3420-3432.

List, F., Bocola, M., Haeger, M. C. & Sterner, R. (2012). Constitutively active glutaminase variants provide insights into the activation mechanism of anthranilate synthase. Biochemistry 51, 2812-2818.

Guldan, H., Matysik, F. M., Bocola, M., Sterner, R. & Babinger, P. (2011). Functional assignment of an enzyme that catalyzes the synthesis of an archaea-type ether lipid in bacteria. Angew. Chem. Int. Ed. Engl. 50, 8188-8191.

Fischer, A., Seitz, T., Lochner, A., Sterner, R., Merkl, R. & Bocola, M. (2011). A fast and precise approach for computational saturation mutagenesis and its experimental validation by using an artificial (βα)₈-barrel protein. ChemBioChem 12, 1544-1550.

Schwab, T. & Sterner, R. (2011). Stabilization of a metabolic enzyme by library selection in Thermus thermophilus. ChemBioChem 12, 1581-1588.

2010 - 2009

Ehrmann, A., Richter, K., Busch, F., Reimann, J., Albers, S.V. & Sterner, R. (2010). Ligand-inducted formation of a transient tryptophan synthase complex with αββ subunit stoichiometry. Biochemistry 49, 10842-10853.

B Mandach, C. & Merkl R. (2010) Genes optimized by evolution for accurate and fast translation encode in Archaea and Bacteria a braod and characteristic spectrum of protein functions. MC Genomics 11, 617.

Liebold, C., List, F., Kalbitzer, H.R., Sterner, R. & Brunner, E. (2010). The interaction of ammonia and xenon with the imidazole glycerol phosphate synthase from Thermotoga maritima as detected by NMR spectroscopy. Protein Sci. 19, 1774-1782.

Richter, M., Bosnali, M., Carstensen, L., Seitz, T., Durchschlag, H., Blanquart, S., Merkl, R. & Sterner, R. (2010). Computational and experimental evidence for the evolution of a (βα)₈-barrel protein from an ancestral quarter-barrel stabilised by disulfide bonds. J. Mol. Biol. 398, 763-773.

Drzewiecki, K., Angelov, A., Ballschmiter, M. Tiefenbach, K.-J., Sterner, R. & Liebl, W. (2010) Hyperthermostable acetyl xylan esterase. Microbial Biotechnol. 3, 84-92.

Merkl R, Wiezer A. (2009) GO4genome: A prokaryotic phylogeny based on genome organization. J. Mol. Evol. 68, 550-562.

Schlee, S., Deuss, M., Bruning, M., Ivens, A., Schwab, T., Hellmann, N., Mayans, O. & Sterner, R. (2009). Activation of anthranilate phosphoribosyl transferase from Sulfolobus solfataricus by removal of Mg-inhibition and acceleration of product release. Biochemistry 48, 5199-5209.

Claren, J., Malisi, C., Höcker, B. & Sterner, R. (2009). Establishing wild-type levels of catalytic activity on natural and artificial (βα)₈-barrel protein scaffolds. Proc. Natl. Acad. Sci. USA 106, 3704-3709.

Xiang, D. F., Kolb, P., Meier, M. M., Fedorov, E. V., Fedorov, A. A., Sterner, R., Almo S. C., Shoichet, B. K. & Raushel, F. M. (2009). Functional annotation and three-dimensional structure of Dr0930 from Deinococcus radiodurans: A close relative of phosphotriesterase in the amidohydrolase family. Biochemistry 48, 2237-2247.

Fischer, A., Enkler, N., Neudert, G., Bocola, M., Sterner, R. & Merkl, R. (2009). TransCent: Computational enzyme design by transferring active sites and considering constraints relevant for catalysis. BMC Bioinformatics 10, 54.

Seitz, T., Thoma, R., Schoch, G.A., Stihle, M., Benz, J., D'Arcy, B., Wiget, A., Ruf, A., Hennig, M. & Sterner, R. (2010). Enhancing the stability and solubility of the glucocorticoid receptor ligand-binding domain by high-throughput library screening. J. Mol. Biol. 403, 562-577.

Höcker, B., Lochner, A., Seitz, T., Claren, J. & Sterner, R. (2009). High-resolution crystal structure of an artificial (βα)₈-barrel protein designed from identical half-barrels. Biochemistry 48, 1145-1147.

2008 - 2006

Guldan, H., Sterner, R. & Babinger, P. (2008). Identification and Characterization of a Bacterial Glycerol-1-phosphate Dehydrogenase: Ni²⁺ -Dependent AraM from Bacillus subtilis. Biochemistry 47, 7376-7384.

Merkl, R. & Zwick, M. (2008). H2r:Identification of evolutionary important residues by means of an entropy based analysis of multiple sequence alignments . BMC Bioinformatics 9, 151.

Reetz, M. T., Rentzsch, M., Pletsch, A., Taglieber, A., Hollmann, F., Mondière, R. J. G., Dickmann, N., Höcker, B., Cerrone, S., Haeger, M. C. & Sterner, R. (2008). A Robust Protein Host for Anchoring Chelating Ligands and Organocatalysts. ChemBioChem 9, 552-564.

Schwab, T., Skegro, D., Mayans, O. & Sterner, R. (2008). A rationally designed monomeric variant of anthranilate phosphoribosyltransferase from Sulfolobus solfataricus is as active as the dimeric wild-type enzyme but less thermostable. J. Mol. Biol. 376, 506-516.

Seitz, T., Bocola, M., Claren, J. & Sterner, R. (2007). Stabilization of a (βα)₈-Barrel Protein Designed from Identical Half Barrels. J. Mol. Biol. 372, 114-129.

Merkl, R. (2007). Modelling the evolution of the archeal tryptophan synthase . BMC Evol Biol. 7, 59.

Merkl, R. (2006). AMIGOS: a method for the inspection of genomic organisation or structure and its application to characterise conserved gene arrangements . In Silico Biol. 6, 281-306.

Waack, S., Keller, O., Asper, R., Brodag, T., Damm, C., Fricke, W. F., Surovcik, K., Meinicke, P. & Merkl, R. (2006). Score-based prediction of genomic islands in prokaryotic genomes using hidden Markov models. BMC Bioinformatics 7, 142.

Merkl, R. (2006). A comparative categorization of protein function encoded in bacterial or archeal genomic islands . J Mol Evol. 62, 1-14.

Leopoldseder, S., Hettwer, S. & Sterner, R. (2006). Evolution of Multi-Enzyme Complexes: The Case of Tryptophan Synthase. Biochemistry 45, 14111-14119.

Marino, M., Deuss, M., Svergun, D., Konarev, P., Sterner, R. & Mayans, O. (2006). Structural and Mutational Analysis of Substrate Complexation by Anthranilate Phosphoribosyltransferase from Sulfolobus solfataricus. J. Biol. Chem. 281, 21410-21421.

2005 - 2003

Schneider, B., Knöchel, T., Darimont, B., Hennig, M., Dietrich, S., Babinger, K., Kirschner, K. & Sterner, R. (2005). Role of the N-terminal Extension of the (βα)₈-Barrel Enzyme Indole-3-Glycerol Phosphate Synthase for its Fold, Stability and Catalytic Activity. Biochemistry 44, 16405-16412.

Vega, C., Zou, P., Fernandez, F., Murphy, G., Sterner, R., Popov, A. & Wilmanns, M. (2005). Regulation of the hetero-octameric ATP phosphoribosyl transferase complex from Thermotoga maritima by a tRNA-synthetase-like subunit. Mol. Microbiol. 55, 675-686.

Wiezer, A. & Merkl, R. (2005). A comparative categorization of gene flux in diverse microbial species . Genomics 86, 462-475.

Höcker, B., Claren, J. & Sterner, R. (2004). Mimicking enzyme evolution by generating new (βα)₈-barrels from (βα)₄-half-barrels. Proc. Natl. Acad. Sci. USA 101, 16448-16453.

Thiemann, V., Dönges, C., Prowe, S., Sterner, R. & Antranikian, G. (2004). Characterisation of a thermoalkali-stable cyclodextrin glycosyltransferase from the anaerobic thermoalkaliphilic bacterium Anaerobranca gottschalkii. Arch. Microbiol. 182, 226-235.

Leopoldseder, S., Claren, J., Jürgens, C. & Sterner, R. (2004). Interconverting the catalytic activities of (βα)₈-barrel enzymes from different metabolic pathways: sequence requirements and molecular analysis. J. Mol. Biol. 337, 871-879.

Meinicke, P., Tech, M., Morgenstern, B. & Merkl, R. (2004). Oligo kernels for datamining on biological sequences: a case study on prokaryotic translation initiation sites . BMC Bioinformatics 5, 169.

Veith, B., Herzberg, C., Steckel, S., Feesche, J., Maurer, K. H., Ehrenreich, P., Bäumer, S., Henne, A., Liesegang, H., Merkl, R., Ehrenreich, A. & Gottschalk, G. (2004). The complete genome sequence of Bacillus licheniformis DSM13, an organism with great industrial potential. J Mol Microbiol Biotechnol. 7, 204-211.

Merkl, R. (2004). SIGI: score-based identification of genomic islands . BMC Bioinformatics 5, 22.

Henne, A., Brüggemann, H., Raasch, C., Wiezer, A., Hartsch, T., Liesegang, H., Johann, A., Lienard, T., Gohl, O., Martinez-Arias, R., Jacobi, C., Starkuviene, V., Schlenczeck, S., Dencker, S., Huber, R., Klenk, H. P., Kramer W., Merkl, R., Gottschalk, G., & Fritz, H.J.(2004). The genome sequence of the extreme thermophile Thermus thermophilus. Nat. Biotechnol. 22, 547-553.

Helmstaedt, K., Heinrich, G., Merkl, R. & Braus, G. H. (2004). Chorismate mutase of Thermus thermophilus is a monofunctional AroH class enzyme inhibited by tyrosine. Arch Microbiol. 181, 195-203.

Tech, M. & Merkl, R. (2003). YACOP: Enhanced gene prediction obtained by a combination of existing methods . In Silico Biol. 3, 441-451.

Merkl, R. (2003). A survey of codon and amino acid frequency bias in microbial genomes focusing on translational efficiency . J Mol Evol. 57, 453-466.

Wiezer, A. & Merkl, R. (2003). secureBLAST. In Silico Biol. 3, 405-409.

Bruggemann, H., Baumer, S., Fricke, W. F., Wiezer, A., Liesegang, H., Decker, I., Herzber, C., Martinez-Arias, R., Merkl, R., Henne, A. & Gottschalk, G. (2003). The genome sequence of Clostridium tetani, the causative agent of tetanus disease. Proc Natl Acad Sci U S A 100, 1316-1321.

2002 - 2000

Henn-Sax, M., Thoma, R., Schmidt, S., Hennig, M., Kirschner, K. & Sterner, R. (2002). Two (βα)₈-barrel enzymes of histidine and tryptophan biosynthesis have similar reaction mechanisms and common strategies for protecting their labile substrates. Biochemistry 41, 12032-12042.

Hettwer, S. & Sterner, R. (2002). A novel tryptophan synthase β-subunit from the hyperthermophile Thermotoga maritima: quaternary structure, steady-state kinetics, and putative physiological role. J. Biol. Chem. 277, 8194-8201.

Douangamath, A., Walker, M., Beismann-Driemeyer, S., Vega-Fernandez, M.C., Sterner, S. & Wilmanns, M. (2002). Structural evidence for ammonia tunnelling across the (βα)₈-barrel of the imidazole glycerol phosphate synthase bienzyme complex. Structure 10, 185-193.

Höcker, B., Schmidt, S. & Sterner, R. (2002). A common evolutionary origin of two elementary enzyme folds. FEBS letters 510, 133-135.

Larbig, K. D., Christmann, A., Johann, A., Klockgether, J., Hartsch, T., Merkl, R., Wiehlmann, L., Fritz, H. J. & Tümmler, B. (2002). Gene islands integrated into tRNA(Gly) genes confer genome diversity on a Pseudomonas aeruginosa clone. J Bacteriol. 184, 6665-6680.

Deppenmeier, U., Johann, A., Hartsch, T., Merkl, R., Schmitz, R. A., Martinez-Arias, R., Henne, A., Wiezer, A., Bäumer, S., Jacobi, C., Brüggemann, H., Lienard, T., Christmann, A., Bömeke, M., Steckel, S., Bhattacharyya, A., Lykidis, A., Overbeek, R., Klenk, H. P., Gunsalus, R. P., Fritz, H. J. & Gottschalk, G. (2002). The genome of Methanosarcina mazei: evidence for lateral gene transfer between bacteria and archaea. J Mol Microbiol Biotechnol. 4, 453-461.

Beismann-Driemeyer, S. & Sterner, R. (2001). Imidazole glycerol phosphate synthase from Thermotoga maritima: Quaternary structure, steady-state kinetics and reaction mechanism of the bi-enzyme complex. J. Biol. Chem. 276, 20387-20996.

Höcker, B., Beismann-Driemeyer, S., Hettwer, S., Lustig, A. & Sterner, R. (2001). Dissection of a (βα)₈-barrel enzyme into two folded halves. Nat. Struct. Biol. 8, 32-36.

Lang, D., Thoma, R., Henn-Sax, M., Sterner, R. & Wilmanns, M. (2000). Structural evidence for evolution of the β/α barrel scaffold by gene duplication and fusion. Science 289, 1546-1550.

Jürgens, C., Strom, A., Wegener, D., Hettwer, S., Wilmanns, M. & Sterner, R. (2000). Directed evolution of a (βα)₈-barrel enzyme to catalyze related reactions in two different metabolic pathways. Proc. Natl. Acad. Sci. USA 97, 9925-9930.

Thoma, R., Hennig, M., Sterner, R. & Kirschner, K. (2000). Structure and function of mutationally generated monomers of dimeric phosphoribosylanthranilate isomerase from Thermotoga maritima. Structure 8, 265-276.

Reviews

Merkl, R. & Sterner, R. (2016). Ancestral protein reconstruction: techniques and applications. Biol. Chem. 397, 1-21.

List, F., Sterner, R. & Wilmanns, M. (2011). Related (βα)₈-barrel proteins in histidine and tryptophan biosynthesis: a paradigm to study enzyme evolution. ChemBioChem 12, 1487-1494.

Sterner, R. & Brunner, E. The relationship between catalytic activity, structural flexibility and conformational stability as deduced from the analysis of mesophilic - thermophilic enzyme pairs and protein engineering studies. In: F. Robb et al., eds., Thermophiles - Biology and Technology at High Temperatures, CRC Press, Boca Raton, London, New York, pp. 25-38, 2008.

Sterner, R. & Höcker, B. (2005). Catalytic versatility , stability, and evolution of the (βα)₈-barrel enzyme fold. Chemical Reviews 105, 4038-4055.

Jaenicke, R. & Sterner, R. Life at high temperatures. In: M. Dworkin et al., eds., The Procaryotes: An Evolving Electronic Resource for the Microbiological Community, 3rd edition (Latest update release 3.9, March 2002), New York, Springer-Verlag, 2000.

Sterner, R. & Liebl, W. (2001). Thermophilic Adaptation of Proteins. Crit. Rev. Biochem. Mol. Biol. 63, 39-106.

Sterner, R., Merz, A., Thoma, R. & Kirschner, K. (2001). Phosphoribosyl anthranilate isomerase and indoleglycerol phosphate synthase: tryptophan biosynthetic enzymes from Thermotoga maritima. Meth. Enzymol. 331, 270-280.

Sterner, R. (2001). 4Fe-4S ferredoxin from Thermotoga maritima. Meth. Enzymol. 334, 23-30.

Höcker, B., Jürgens, C., Wilmanns, M. & Sterner, R. (2001). Stability, catalytic versatility and evolution of the (βα)₈-barrel fold. Curr. Opin. Biotechnol. 12, 376-381.

Henn-Sax, M., Höcker, B., Wilmanns, M. & Sterner, R. (2001). Divergent evolution of (βα)₈-barrel enzymes. Biol. Chem. 382, 1315-1317.

Others

Meeting reports, books, book reviews, guest editorials

Claren, J., Schwab, T. & Sterner, R. (2018). Library generation and auxotrophic selection assays in Escherichia coli and Thermus thermophilus. Methods Mol Biol, 1685, 333-345.

Merkl, R. (2015) Bioinformatik: Grundlagen, Algorithmen, Anwendungen. Wiley-VCH, Weinheim.

Sterner, R. (2011). Directed evolution: a powerful approach to optimising and understanding enzymes. C hemBioChem 12, 1439-1440.

Merkl, R. & Waack, Stephan (2009) Bioinformatik Interaktiv: Algorithmen und Praxis. Wiley-Blackwell, Weinheim.

Sterner, R., Merkl, R. & Raushel, F.M. (2008). Computational Design of Enzymes. Chem. Biol. 5, 421-423.

Sterner, R. & Skerra, A. (2007). Design von Enzymen und anderen Proteinen: Einblicke aus Natur, Labor und Computersimulationen. Biospektrum 07, 814.

Sterner, R. & Schmid, F.X. (2004). De novo design of an enzyme. Science 304, 1916-1917.

Jaenicke, R. & Sterner, R. (2003). Protein Design at the Crossroads of Biotechnology, Chemistry, Theory, and Evolution. Futura 18, 5-10.

Jaenicke, R. & Sterner, R. (2003). Protein Design at the Crossroads of Biotechnology, Chemistry, Theory, and Evolution. Angew. Chem. Int. Ed. 42, 140-142.

Sterner, R. (2003). Book Review: Directed Molecular Evolution of Proteins or How to Improve Enzymes for Biocatalysis. Edited by S. Brakmann and K. Johnsson. ChemBioChem 4, 119.

Schmid, F.X. & Sterner, R. (2004). Protein Design. ChemBioChem 5, 143-144.

contact

Prof. Dr. Reinhard Sterner

Institute of Biophysics and Physical Biochemistry
Room Nr. E3_1.313

Address:
University of Regensburg
Universitätsstrasse 31
93053 Regensburg

Postal Address:
University of Regensburg
93040 Regensburg

Secretary:
Claudia Pauer
Room Nr. E3_1.311
Phone +49-941-943 3004
Fax +49-941-943 2813

Our Department is located in the first floor of the new building WNE3.