Struktur und Funktion der Proteine

Der Schlüssel zu neuen Angriffspunkten gegen Krankheitserreger steckt im Detail, genauer: in Proteinen, über die die Krankheitserreger mit ihren Wirten in Kontakt treten oder die sie für lebenswichtige Stoffwechselprozesse benötigen. Die Wirkungsweise dieser Eiweißstoffe lässt sich verstehen, wenn man ihre dreidimensionale Struktur kennt. Unsere Wissenschaftler setzen hierfür moderne Techniken wie die Röntgenstrukturanalyse, Kernresonanzspektroskopie (NMR) und Massenspektrometrie ein.

Team

    Prof. Wulf Blankenfeldt

    Wulf Blankenfeldt

    Abteilungsleiter

    0531 6181-7000

    Kontakt


    Publikationen

    A. Research Papers:

    55. C. Feiler, A.C. Fisher, M.J. Marrichi, L. Wright, P.A.M. Schmidpeter, W. Blankenfeldt, M. Pavelka, M.P. DeLisa (2013). Directed evolution of Mycobacterium tuberculosis beta-lactamase reveals gatekeeper residue that controls drug resistance and catalytic efficiency. PLoS ONE 8(9): e73123. PubMed

    54. N. Xu, E.G. Ahuja, P. Janning, D.V. Mavrodi, L.S. Thomashow, W. Blankenfeldt (2013). Trapped intermediates in crystals of the FMN-dependent oxidase PhzG provide insight into the final steps of phenazine biosynthesis. Acta Cryst. D69: 1403-13. PubMed

    53. D.V. Mavrodi, J.A. Parejko, O.V. Mavrodi, Y.S. Kwak, D.M. Weller, W. Blankenfeldt, L.S. Thomashow. (2013). Recent insights into the diversity, frequency and ecological roles of phenazines in fluorescent Pseudomonas spp. Environ. Microbiol. 15:675-86. PubMed

    52. A. Hoeppner, F. Thomas, A. Rueppel, R. Hensel, W. Blankenfeldt, P. Bayer, A. Faust. (2012). Structure of the corrinoid:coenzyme M methyltransferase MtaA from Methanosarcina mazei. Acta Cryst. D68: 1549-57. PubMed

    51. E.A. Stigter, Z. Guo, R.S. Bon, Y.W. Wu, A. Choidas, A. Wolf, S. Menninger, H. Waldmann, W. Blankenfeldt*, R.S. Goody* (2012). Development of Selective, Potent RabGGTase Inhibitors. J. Med. Chem. 55: 8330-40. *corresponding authors PubMed

    50. N. Xu, S. Yu, S. Moniot, M. Weyand, W. Blankenfeldt (2012). Crystallization and preliminary crystal structure analysis of the ligand-binding domain of PqsR (MvfR), the Pseudomonas Quinolone Signal (PQS) responsive quorum sensing transcription factor of Pseudomonas aeruginosa. Acta Cryst. F68: 1034-9. PubMed

    49. C. Deraeve, Z. Guo, R.S. Bon, W. Blankenfeldt, R. Dilucrezia, A. Wolf, S. Menninger, E.A. Stigter, S. Wetzel, A. Choidas, K. Alexandrov, H. Waldmann, R.S. Goody, Y.W. Wu (2012). Psoromic Acid is a Selective and Covalent Rab-Prenylation Inhibitor Targeting Autoinhibited RabGGTase.  J. Am. Chem. Soc. 134:7384-91. PubMed

    48. J.W. Mueller, N.M. Link, A. Matena, L. Hoppstock, A. Rüppel, P. Bayer, W. Blankenfeldt (2011). Crystallographic proof for an extended hydrogen-bonding network in small prolyl isomerases. J. Am. Chem. Soc. 133:20096-9.PubMed

    47. J. Bigalke, S.A. Dames, W. Blankenfeldt, S. Grzesiek, M. Geyer (2011). Structure and Dynamics of a Stabilized Coiled-Coil Domain in the P-TEFb Regulator Hexim1. J. Mol. Biol. 414:639-53. PubMed

    46. S. Yu, A. Vit, S. Devenish, H.K. Mahanty, A. Itzen, R.S. Goody, W. Blankenfeldt (2011). Atomic resolution structure of EhpR: phenazine resistance in Enterobacter agglomerans Eh1087 follows principles of bleomycin / mitomycin C resistance in other bacteria. BMC Struct. Biol. 11:33. PubMed

    45 S. Waldmüller, J. Erdmann, P. Binner, G. Gelbrich, S. Pankuweit, C. Geier, B. Timmermann, J. Haremzy, A. Perrot, S. Scheer, R. Wacher, N. Schulze-Waltrup, A. Demintzoglou, J. Schönberger, W. Zeh, B. Jurmann, T. Brodherr, J. Börgel, M. Farr, H. Milting, W. Blankenfeldt, R. Reinhardt, C. Ozcelik, K.J. Osterziel, M. Loeffler, B. Maisch, V. Regitz-Zagrosek, H. Schunkert, T. Scheffold (2011). Novel correlations between the genotype and the phenotype of hypertrophic and dilated cardiomyopathy; results from the German Competence Network Heart Failure. Eur J. Heart Fail. 13:1185-92.PubMed

    44. S. Breuer, S.I. Schievink, A. Schulte, W. Blankenfeldt, O.T. Fackler, M. Geyer (2011). Molecular Design, Functional characterization and Structural Basis of a Protein Inhibitor Against the HIV-1 Pathogenicity Factor Nef. PLoS ONE 6:e20033. PubMed

    43. R.S. Bon, Z. Guo, E.A. Stigter, S. Wetzel, S. Menninger, A. Wolf, A. Choidas, K. Alexandtrov, W. Blankenfeldt, R.S. Goody, H. Waldmann (2011). Structure-Guided Development of Selective RabGGTase Inhibitors. Angew. Chem. Int. Ed. Engl 50:4957-61. PubMed

    42. Q.A. Li, D.V. Mavrodi, L.S. Thomashow, M. Roessle, W. Blankenfeldt (2011). Ligand Binding Induces an Ammonia Channel in 2-Amino-2-desoxyisochorismate (ADIC) Synthase PhzE. J. Biol. Chem. 286:18213-21. PubMed

    41. X. Hou, N. Hagemann, S. Schoebel, W. Blankenfeldt, R.S. Goody, K.S. Erdmann, A. Itzen (2011). A Structural Basis for Lowe Syndrome caused by Mutations in the Rab-binding Domain OCRL1. EMBO J 30:1659-70. PubMed

    40. S. Hoffjan, S. Waldmüller, W. Blankenfeldt, J. Kötting, P. Gehle, P. Binner, J.T. Epplen, T. Scheffold (2011). Three novel mutations in the ACTA2 gene in German patients with thoracic aortic aneurysms and dissections. Eur. J. Hum. Gen 19:520-4. PubMed

    39. M.P. Müller#, H. Peters#, J. Blümer, W. Blankenfeldt*, R.S. Goody*, A. Itzen* (2010). The Legionella effector protein DrrA AMPylates the membrane traffic regulator Rab1b. Science 329:946-9.# equal contribution; *corresponding authors PubMed

    38. E.M. Gazdag, I.C. Cirstea, R. Breitling, J. Lukes, W. Blankenfeldt*, K. Alexandrov* (2010). Purification and crystallization of human Cu/Zn superoxide dismutase recombinantly produced in the protozoan Leishmania tarentolae. Acta. Cryst F66:871-7. *corresponding authors PubMed

    37. S. Schoebel, W. Blankenfeldt, RS Goody, A. Itzen (2010). High-affinity binding of phosphatidylinositol 4-phosphate by Legionella pneumophila DrrA. EMBO Rep 11:598-604. PubMed

    36. S. Foldynová-Trantirková, P. Sekyrová, K. Tmejová, E. Brumovská, O. Bernatik, W. Blankenfeldt, P. Krejci, A. Kozubík, T. Dolezal, L. Trantírek, V. Bryia (2010). Breast cancer-specific mutations in CK1epsilon inhibit Wnt/beta-catenin and activate the Wnt/Rac1/JNK and NFAT pathways to decrease cell adhesion and promote cell migration. Breast Cancer Res. 12:R30. PubMed

    35. D.V. Mavrodi, T.L. Peever, O.V. Mavrodi, J.A. Parejko, J.M. Raaijmakers, P. Lemanceau, S. Mazurier, L. Heide, W. Blankenfeldt, D.M. Weller, L.S. Thomashow (2010). Diversity and Evolution of the Phenyzine Biosynthesis Pathway. Appl. Anviron. Microbiol. 76:866-79. PubMed

    34. S. Schoebel, L.K. Oesterlin, W. Blankenfeldt, R.S. Goody, A. Itzen (2009). RabGDI displacement by DrrA from Legionella is a consequence of its guanine nucleotide exchange activity. Mol. Cell. 36:1060-72. PubMed

    33. K.T. Tan, E. Guiu-Rozas, R.S. Bon, Z. Guo, C. Delon, S. Wetzel, S. Arndt, K. Alexandrov, H. Waldmann, R.S. Goody, Y.W. Wu, W. Blankenfeldt (2009). Design, Synthesis and Characterization of Peptide-Based Rab Geranylgeranyl Transferase Inhibitors. J. Med. Chem. 52:8025-37. PubMed

    32. M. Mentel, W. Blankenfeldt*, R. Breinbauer*, (2009). The Active Site of an Enzyme Can Host Both Enantiomers of a Racemic Ligand Simultaneously. Angew. Chem. Int. Ed. Engl. 48:9084-7; *corresponding authors PubMed

    31. F. Vollmuth, W. Blankenfeldt, M. Geyer (2009). Structures of the dual bromodonaims of the P-TEFb activating protein Brd4 at atomic resolution J. Biol. Chem. 284:36547-56. PubMed

    30. V. Sychrovsky, S. Foldynova-Trantirkova, N. Spackova, K. Robeyns, L. van Meervelt, W. Blankenfeldt, Z. Vokacova, J. Sponer, L. Trantirek (2009). Revisiting the planaritz of mucleic acid bases: Pyramidilization at glycosidic nitrogen in purine bases is modulated by orientation of glycosidic torsion. Nucleic Acids Res. 37:7321-31. PubMed

    29. S. Yu, V. Jensen, J. Seeliger, I. Feldmann, S. Weber, E. Schleicher, S. Häussler, W. Blankenfeldt (2009). Structure elucidation and preliminary assessment of hydrolase activity of PqsE, the Pseudomonas quinolone signal (PQS) response protein. Biochemistry 48:10298-307. PubMed

    28. U.T. Nguyen, Z. Guo, C. Delon, Y.W. Wu, C. Deraeve, B. Fränzel, R.S. Bon, W. Blankenfeldt, R.S. Goody, H. Waldmann, D. Wolters, K. Alexandrov (2009). Analysis of the eukaryotic prenylome by isoprenoid affinity tagging. Nat. Chem. Bio. 5:227-35. PubMed

    27. T. Bergbrede, N. Chuky, S. Schoebel, W. Blankenfeldt, M. Geyer, E. Fuchs, R.S. Goody, F. Barr, K. Alexandrov (2009). Biophysical analysis of the interation of Rab6a GTPase with its effector domains. J. Bio. Chem. 284:2628-35.PubMed

    26. E.G. Ahuja, P. Janning, M. Mentel, A. Graebsch, R. Breinbauer, W. Hiller, B. Costisella, L.S. Thomashow, D.V. Mavrodi, W. Blankenfeldt (2008). PhzA/B catalyzes formation of the tricyclic scaffold in phenazine biosynthesis. J. Am. Chem. Soc. 130:17053-61. PubMed

    25. Z. Guo, Y.W. Wu, D. Das, C. Delon, J. Cramer, S. Yu, S. Thuns, N. Lupilova, H. Waldmann, L. Brunsveld, R.S. Goody, K. Alexandrov, W. Blankenfeldt (2008). Structures of RabGGTase:substrate/product complexes provide insights into the evolution of protein prenylation. EMBO J. 27-2444-56. PubMed

    24. Z. Guo, Y.W. Wu, K.T. Tan, R.S. Bon, E. Guio-Rozas, C. Delon, S. Wetzel, S. Arndt, R.S. Goddy, W. Blankenfeldt, K. Alexandrov, H. Walkdmann (2008). Development of Selective RabGGTase Inhibitors and the First Crystal Structure of a RabGGTase Inhibitor Complex. Angew. Chem. Int. Ed. Engl. 47:3747-57. PubMed

    23. B.S. Budde, P. Binner, S. Waldmüller, W. Höhne, W. Blankenfeldt, S. Hassfeld, J. Brömsen, A. Dermintzoglu, M. Wieczorek, E. May, R.S. Goody, H.P. Vosberg, P. Nürnberg, T. Scheffold (2007). A Novel Mutation in the ß-Myosin Heavy Chain Gene (MYH7) is Associated with Left Ventricular Non-Compaction in a Large German Family. PLoS ONE 2:e1362. PubMed

    22. W. Blankenfeldt*, N.H. Thomä, J.S. Wray, M. Gautel, I. Schlichting* (2006). Crystal structures of human cardiac beta-myosin II S2-Delta provide insight into the functional role of the S2 subfragment. Proc. Natl. Acad. Sci. USA 103:17713-17. * corresponding authors PubMed

    21. N. Gohain, L.S. Thomashow, D.V. Mavrodi, W. Blankenfeldt (2006). The purification, crystallization and preliminary structural characterization of FAD-dependent monooxygenase PhzS, a phenzazine-modifying enzyme fromPseudomonas aeruginosa. Acta Cryst F62:989-92. PubMed

    20. N. Gohain, L.S. Thomashow, D.V. Mavrodi, W. Blankenfeldt (2006). The purification, crystallization and preliminary structural characterization of PhzM, a phenazine-modifying methyltransferase from Pseudomonas aeruginosa. Acta Cryst. F62:887-90. PubMed

    19. K. Kühnel, W. Blankenfeldt, J. Terner, I. Schlichting (2006). Crystal structures of chloroperoxidase with its bound substrates and complexed with formate acetate and nitrate. J. Bio. Chem. 281:23990-8. PubMed

    18. P. Herde, W. Blankenfeldt (2006). The purification, crystallization and preliminary structural characterization of human MAWDBP a member of the phenazine biosynthesis-like protein family. Acta. Cryst. F62:546-9. PubMed

    17. W. Blankenfeldt, A.P. Kuzin, T. Skarina, Y. Korniyenko, L. Tong, P. Bayer, P. Janning, L.S. Thomashow, D.V. Mavrodi (2004). Structure and funtion of the phenazine biosynthesis protein PhzF from Pseudomonas fluorescens. Proc. Natl. Acad. Sci USA 101:16431-6. PubMed

    16. E.G. Ahuja, D.V. Mavrodi, L.S. Thomashow, W. Blankenfeldt (2004). Overexpression purification and crystallization of PhzA, the first enzyme of the phenazine biosynthesis pathway of Pseudomonas fluorescens 2-79. Acta. Cryst. D60:1129-31. PubMed

    15. D.V. Mavrodi, N. Bleimling, L.S. Thomashow, W. Blankenfeldt (2004). The purification, crystallization and preliminary structural characterization of PhzF a key enzyme in the phenazine-biosynthesis pathway from Pseudomonas fluorescens 2-79. Acta. Cryst. D60:184-6. PubMed

    14. C. Dong, L.L. Major, A. Allen, W. Blankenfeldt, D. Maskell, J.H. Naismith (2003). High-resolution structures of RmlC from Streptococcus suis in complex with substrate analogs locate the active site of this class of enzyme. Structure (Camb) 11:715-23. PubMed

    13. I.D. Kerr, R.I.M. Wadsworth, L. Cubeddu, W. Blankenfeldt, J.H. Naismith, M.F. White (2003). Insights into ssDNA recognition by the OB fold from a structural and thermodynamic study of Sulfolobus SSB. EMBO J 22:2561-70. PubMed

    12. W. Blankenfeldt, I.D. Kerr, M.F. Giraud, H.J. McMiken, G. Leonard, C. Whitfield, P. Messner, M. Graninger, J.H. Naismith (2002). Variation on a theme of SDR: dTDP-6-deoxy-lyxo-4-hexulose reductase (RmlD) shows a new Mg²+-dependent dimerisation mode in a well-known enzyme family. Structure (Camb) 10:773-86. PubMed

    11. M. Asuncion*, W. Blankenfeldt*, J.N. Barlow, J.H. Naismith (2002). Crystal structure of 3-methylaspartase fromClostridium tetanomorphum. J. Biol. Chem 277:8306-11; *equal contribution PubMed

    10. I.D. Kerr, R.I.M. Wadsworth, W. Blankenfeldt, A.G. Staines, M.F. White, J.H. Naismith (2001). Over-expression purification crystallization and data collection of a single stranded DNA binding protein from Sulfolobus solfataricus. Acta. Cryst. D57:1290-2. PubMed

    9.  M. Asuncion, J.N. Barlow, J. Pollard, A.G. Staines, S. McMahon, W. Blankenfeldt, D. Gani, J.H. Naismith (2001) Over-expression, purification, crystallization and data collection of 3-methylaspartase from Clostridium tetanomorphum. Acta. Cryst. D57_731-3. PubMed

    8.  C. Nowicki, G.R. Hunter, M. Montmartini-Kalisz, W. Blankenfeldt, H.J. Hecht, H. Kalisz (2001). Recominant tyrosine aminotransferase from Trypanosoma cruzi: Structural characterization and site directed mutagenesis of a broad substrate specificity enzyme. Biochim Biophys Acta 1564:268-81. PubMed

    7.  W. Blankenfeldt, M. Asuncion, J.S. Lam, J.H. Naismith (2000). The structural basis of the catalytic mechanism and regulation of glucose-1-phosphate thymidylyltransferase (Rm1A). EMBO J 19:6652-63. PubMed

    6.  W. Blankenfeldt, M.F. Giraud, G. Leonard, R. Rahim, C. Creuzenet, J.S. Lam, J.H. Naismith (2000). The purification, crystallization annd preliminary structural characterization of glucose-1-phosphate thymidylyltransferase (Rm1A), the first enzyme of the dTDP-L-rhamnose synthesis pathway from Pseudomonas aeruginosa. Acta. Cryst. D56_1501-4.PubMed

    5.  W. Blankenfeldt, C. Nowicki, M. Montemartini-Kalisz, H.M. Kalisz, H.J. Hecht (1999). Crystal structure of Trypanosoma cruzi tyrosine aminotransferase: substrate specificity is influenced by cofactor binding mod.e Protein. Sci 8:2406-17.PubMed

    4.  C. Nowicki, M. Montmartini, G.R. Hunter, W. Blankenfeldt, H. Kalisz, H.J. Hecht (1998). Crystallization and preliminary X-ray analysis of tyrosine aminotranferase from Trypanosoma cruzi epimastigotes. Acta Cryst. D54:105-7. PubMed

    3.  D. Völkel, W. Blankenfeldt, D. Schomburg (1998). Large-scale production, purification and refolding of the full length prion protein from Syrian golden hamster in Escherichia coli using the glutathione S-transferase-fusion system. Eur. J. Biochem. 251:462-71. PubMed

    2.  W. Blankenfeldt, J.W. Liao, L.C. Lo, M.C.P. Yeh (1996). Sequential Additions of Nucleophiles to Tricarbonyl(n4-cycloheptadienyl)iron Tetrafluoroborate. Tetrahedron Lett. 37_7361-4. Link

    1.  W. Blankenfeldt, K. Nokihara, S. Naruse, U. Lessel, D. Schomburg, V. Wray (1996). NMR Spectroscopic Evidence that Helodermin, unlike other Members of the Secretin/VIP Family of Peptides, is Substantially Structured in Water. Biochemistry 35:5955-62. PubMed

    B. Reviews:

    5.  A. Itzen, W. Blankenfeldt, R.S. Goody (2011). Adenylylation:Renaissance of a forgotten post-translational modification. Trends Biochem. Sci. 36:221-8. PubMed

    4.  R.S. Goody, M.P. Müller, S. Schoebel, L.K. Oesterlin, J. Blümer, H. Peters, W. Blankenfeldt, A. Itzen (2011). The versatile Legionella effector protein DrrA. Comm. Integ. Biol 4:1-3. PubMed

    3.  M. Mentel, E.G. Ahuja, D.V. Mavrodi, R. Breinbauer, L.S. Thomashow, W. Blankenfeldt (2009). Of Two Make One: The Biosynthesis of Phenazines. ChemBiochem 10:2295-304. PubMed

    2.  D.V. Mavrodi, W. Blankenfeldt, L.S. Thomashow (2006). Phenazine Compounds in Fluoroscent Pseudomonas spp.. Annu. Rev. Phytochemistry 44:417-45. PubMed

    1.  C. Dong, K. Beis, M.F. Giraud, W. Blankenfeldt, S. Allard, L.L. Major, I.D. Kerr, C. Whitfield, J.H. Naismith (2003). A structural perspective on the enzymes that convert dTDP-D-glucose into dTDP-L-rhamnose. Biochem. Soc. Trans. 31:532-6. PubMed

    C. Book Chapters:

    3. W. Blankenfeldt (2013). The Biosynthesis of Phenazines. In: S. Chincholkar, L. Thomashow (eds.). Microbial Phenazines: Biosynthesis, Agriculture and Health. Springer:1-17. Springer

    2. K. Alexandrov, Y.W. Wu, W. Blankenfeldt, H. Waldmann, R.S. Goody (2011). Organization and Function of the Rab Prenylation and Recycling Machinery. In: F. Tamanoi, C.A. Hrycyna, M.O. Bergo (eds.). The Enzyme, Vol. 29: Protein Prenylation PART A. Academic Press:147-62. ScienceDirect

    1. D.V. Mavrodi, L. Thomashow, W. Blankenfeldt (2008). Biosynthesis and regulation of phenazine compounds inPseudomonas spp. In: B. Rehm (ed.). Pseudomonas: Model Organism, Pathogen, Cell Factory. Wiley-VCH. Weinheim:331-52. Wiley Online Library

    D. Patents:

    W. Blankenfeldt, J.H. Naismith (2001). Crystallisation and Functional Analysis of Glucose-1-phosphate Thymidylyltransferase (RmlA) from Pseudomonas aeruginosa. Patent WO/2002/006509

     

     

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