Dr. Markus Perbandt Universität Hamburg Department Chemie Laboratorium für Strukturbiologie von Infektion und Entzündung c/o DESY, Geb. 22a Notkestr. 85 - 20146 Hamburg Telefon: 040 / 8998 - 4745, Fax: - 4747 E-Mail: perbandt(at)chemie.uni-hamburg.de Wissenschaftlicher Werdegang: Studium der Biochemie/Molekularbiologie an der Universität Hamburg (Diplom 1995);  Promotion (1999) am Institut für Biochemie der Freien Universität Berlin (Prof. V.A. Erdmann); Wissenschaftlicher Mitarbeiter am Universitätskrankenhaus Hamburg-Eppendorf, Zentrum für Experimentelle Medizin, Prof. Dr. Dr. Ch. Betzel (1999-2000);  Wissenschaftlicher Mitarbeiter am Massachusetts Institute of Technology, Boston, USA, Prof. Dr. A. Rich (2000); Wissenschaftlicher Mitarbeiter am Institut für Biochemie und Molekularbiologie der Universität Hamburg, Prof. Dr. Dr. Ch. Betzel (2001-2007); Wissenschaftlicher Mitarbeiter am Institut für Biochemie der Universität zu Lübeck, Prof. Dr. R. Hilgenfeld (2007-2009); Wissenschaftlicher Mitarbeiter am Institut für Biochemie und Molekularbiologie der Universität Hamburg, Prof. Dr. Dr. Ch. Betzel (since 2009). Mitgliedschaft in wissenschaftlichen Organisationen: Gesellschaft für Biochemie und Molekularbiologie (GMB), Deutsche Gesellschaft für Kristallographie (DGK), American Society for Biochemistry and Molecular Biology (ASBMB), Deutsche Gesellschaft für Parasitologie (DGP) Funktionen: Koordinator des Konsortiums Hamburg-Lübeck für Experimente am Meßplatz X13 (EMBL/ HASYLAB), Mitglied des HASYLAB User Committees (2005-2008), Mitglied des wissenschaftlichen Ausschusses des DESY (2006-2008), Koordinator Lehre der Graduiertenschule "Structure and Dynamics in Infection - SDI" (seit 2009) Kooperationen: Universität Münster (Prof. E. Liebau), Freie Universität Berlin (Prof. V.A. Erdmann), Christian-Albrechts-Universität zu Kiel (Prof. S. Rose-John, Prof. J. Grötzinger), All India Institute of Medical Sciences (Prof. T.P. Singh), Universität Rom/Italien (Prof. G. Ricci)

---

Forschungsgebiet

Strukturbasiertes Wirkstoff- und Ligandendesign - Schwerpunkt eukaryontische Parasiten -

Das strukturbasierte Wirkstoff- und Ligandendesign geht von der zentralen Annahme aus, dass die Inhibitoren oder Liganden an ein molekulares Target binden. Die Voraussetzung für eine starke Bindung ist eine möglichst weitgehende strukturelle und chemische Komplementarität zwischen dem Zielprotein und dem Liganden/Inhibitor. Das strukturbasierte Wirkstoffdesign ist also die Suche nach einem kleinen Molekül, das möglichst perfekt in die Bindungstasche des Zielproteins hineinpaßt.

Für die Entwicklung von spezifischen Inhibitoren oder Wirkstoffen gegen Erkrankungen oder Infektionen ist es von besonderer Bedeutung das molekulare Target (oder auch Schlüsselenzym) bei hoher Auflösung zu charakterisieren. Um das zu erreichen, werden die Biomolekle kristallisiert und mittels Rötgenstrukturanalyse untersucht. Mittels dieser Erkenntnisse lassen sich dann die Bindungstaschen genauestens beschreiben und die strukturellen Anforderungen für die Inhibitoren bestimmen. Diese Inhibitoren oder Wirkstoffe müssen eben besonders spezifisch gegen das molekulare Targetgerichtet sein, um Wechselwirkungen mit anderen Protein, und damit potentielle Nebenwirkungen, möglichst auszuschließen. Insbesondere ist dies bei der Entwicklung von spezifischen Inhibitoren gegen Viren, Bakterien oder Parasiten von Bedeutung, denn schließlich soll ja der Erreger der Infektion und nicht der Mensch geschädigt werden.

Selbstverständlich findet das strukturbasierte Ligandendesign nicht nur in der Medizin seine Anwendung. Auch bei der Weiterentwicklung von hochaffinen Peptiden gegen bestimmte Biomoleküle kann die Strukturanalyse wertvolle Dienste leisten, um zielgerichtet die Bindungsstärke zu modulieren. [mehr]

Publikationen

Vollständiges Verzeichnis der Veröffentlichungen (über 50 begutachtete Publikationen)

2008

D. Georgieva, A. Kardas, F. Buck, M. Perbandt, and Ch. Betzel. Isolation, crystallization and preliminary X-ray diffraction analysis of L-amino-acid oxidase from Vipera ammodytes ammodytes venom. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 964:918-921 (2008)

E. Liebau, J. Höppner, M. Mühlmeister, C. Burmeister, K. Lüersen, M. Perbandt, C. Schmetz, D. Büttner and N. Brattig. The secretory omega-class glutathione transferase OvGST3 from the human pathogenic parasite Onchocerca volvulus. FEBS J. 5, 3438-3453 (2008)

P. Sharma, N. Singh, M. Sinha, S. Sharma, M. Perbandt, C. Betzel, P. Kaur, A. Srinivasan, and T.P. Singh. Crystal structure of the peptidoglycan recognition protein at 1.8 A resolution reveals dual strategy to combat infection through two independent functional homodimers. J. Mol. Biol. 378:921-930 (2008)

M. Perbandt, J. Höppner, C. Burmeister, K. Lüersen, C. Betzel, and E. Liebau. Structure of the extracellular Prostaglandin D Synthase from the human pathogenic parasite Onchocerca volvulus. J. Mol. Biol. 377, 501-511 (2008)

C. Förster, A. Zerressen-Harte, J.P. Fürste, M. Perbandt, C. Betzel, and V.A. Erdmann. Comparative X-ray structure analysis of human and Escherichia coli tRNA(Gly) acceptor stem microhelices. Biochem. Biophys. Res. Commun. 368: 1002-1006 (2008)

C. Förster, M. Mankowska, J.P. Fürste, M. Perbandt, C. Betzel, and V.A. Erdmann. Crystal structure of a human tRNA(Gly) microhelix at 1.2A resolution. Biochem. Biophys. Res. Commun. 368:996-1001 (2008)

2007

C. Forster, A.B. Brauer, D. Lehmann, T. Borowski, S. Brode, J.P. Fürste, M. Perbandt, C. Betzel, and V.A. Erdmann. Cocrystallizing natural RNA with its unnatural mirror image: biochemical and preliminary X-ray diffraction analysis of a 5S rRNA A-helix racemate. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 63:839-843 (2007)

C. Forster, A.B. Brauer, M. Perbandt, D. Lehmann, J.P. Furste, C. Betzel, V.A. Erdmann Crystal structure of an Escherichia coli tRNA(Gly) microhelix at 2.0A resolution. Biochem. Biophys. Res. Commun. 363:621-625 (2007).

S. Bolik, M. Rubhausen, S. Binder, B. Schulz, M. Perbandt, N. Genov, V.A. Erdmann, S. Klussmann, C. Betzel. First experimental evidence for the preferential stabilization of the natural D- over the nonnatural L-configuration in nucleic acids. RNA 11:1877-1880 (2007)

C. Forster, K. Szkaradkiewicz, M. Perbandt, A.B. Brauer, T. Borowski, J.P. Furste, C. Betzel, V.A. Erdmann. Human tRNA(Gly) acceptor-stem microhelix: crystallization and preliminary X-ray diffraction analysis at 1.2 A resolution. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 63:858-861 (2007)

C. Forster, A.B. Brauer, D Lehmann, T. Borowski, S. Brode, J.P. Furste, M. Perbandt, C. Betzel, V.A. Erdmann. Cocrystallizing natural RNA with its unnatural mirror image: biochemical and preliminary X-ray diffraction analysis of a 5S rRNA A-helix racemate. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 63:839-843 (2007)

C. Forster, A.B. Brauer, M. Perbandt, D. Lehmann, J.P. Furste, C. Betzel, V.A. Erdmann. Crystal structure of an Escherichia coli tRNA(Gly) microhelix at 2.0A resolution. Biochem. Biophys. Res. Commun. 363:621-625 (2007)

M. Perbandt, O. Bruns, M. Vallazza, T. Lamla, C. Betzel, VA. Erdmann. High resolution structure of streptavidin in complex with a novel high affinity peptide tag mimicking the biotin binding motif. Proteins: Structure, Function and Genetics. 67:1147-1153 (2007)

M. Sherawat, P. Kaur, M. Perbandt, C. Betzel, WA. Slusarchyk, GS. Bisacchi, C. Chang, BL. Jacobson, HM. Einspahr, TP. Singh. Structure of the complex of trypsin with a highly potent synthetic inhibitor at 0.97 A resolution. Acta Crystallogr. D Biol. Crystallogr. 63:500-507 (2007)

J.H. Hehemann, L. Redecke, M. Perbandt, R. Saborowski, C. Betzel. Crystallization and preliminary X-ray diffraction studies of trypsin-like proteases from the gastric fluid of the marine crab Cancer pagurus. Acta Crystallogr. F Struct. Biol. Cryst. Commun. 63:242-245 (2007)

C. Forster, M. Perbandt, A.B. Brauer, S. Brode, J.P Furste, C. Betzel, VA. Erdmann. Crystallization and preliminary X-ray diffraction analysis of an Escherichia coli tRNA(Gly) acceptor-stem microhelix. Acta Crystallogr. F Struct. Biol. Cryst. Commun. 63:46-48 (2007)

2006

N. Singh, T. Jabeen, A. Pal, S. Sharma, M. Perbandt, C. Betzel, TP. Singh. Crystal structures of the complexes of a group IIA phospholipase A2 with two natural anti-inflammatory agents, anisic acid, and atropine reveal a similar mode of binding. Proteins: Structure Function and Bioinformatics 64:89-100 (2006)

W.R. Rypniewski, M. Vallazza, M. Perbandt, S. Klussmann, L.J. deLucas, C. Betzel, V.A. Erdmann. The first crystal structure of an RNA racemate. Acta Crystallogr. D Biol. Crystallogr. 62:659-664 (2006)

C. Forster, N. Krauss, A.B. Brauer, K. Szkaradkiewicz, S. Brode, K. Hennig, J.P Furste, M. Perbandt, C. Betzel, V.A. Erdmann. Crystallization and preliminary X-ray diffraction analysis of a tRNASer acceptor-stem microhelix. Acta Crystallogr. F Struct. Biol. Cryst. Commun. 62:559-561 (2006)

C. Forster, A.B. Brauer, S. Brode, K.S. Schmidt, M. Perbandt, A. Meyer, W.R. Rypniewski, C. Betzel, J. Kurreck, J.P Furste, V.A. Erdmann. Comparative crystallization and preliminary X-ray diffraction studies of locked nucleic acid and RNA stems of a tenascin C-binding aptamer. Acta Crystallogr. F Struct. Biol. Cryst. Commun. 62:665-668 (2006)

2005

R. Czaja, M. Perbandt, C. Betzel, U. Hahn. Purine activity of RNase T1RV is further improved by substitution of Trp59 by tyrosine. Biochem. Biophys. Res. Commun. 336:882-889 (2005)

S. Bilgrami, S. Yadav, P. Kaur, S. Sharma, M. Perbandt, C. Betzel, T.P. Singh. Crystal Structure of the Disintegrin Heterodimer from Saw-Scaled Viper (Echis carinatus) at 1.9 A Resolution. Biochemistry  44(33):11058-11066 (2005)

E. Liebau, F. De Maria, C. Burmeister, M. Perbandt, P. Turella, G. Antonini, G. Federici, F. Giansanti, L. Stella, M. Lo Bello, A.M. Caccuri, G. Ricci. Cooperativity and pseudo-cooperativity in the glutathione S-transferase from Plasmodium falciparum. J. Biol. Chem. 280:26121-26128 (2005)

T. Jabeen, S. Sharma, N. Singh, R. K. Singh, P. Kaur, M. Perbandt, Ch. Betzel, A. Srinivasan and T. P. Singh. Crystal structure of a calcium - induced dimer of two isoforms of cobra phospholipase A2 at 1.6 Å resolution. Proteins: Structure, Function and Genetics 59:856-863 (2005)

L. Redecke, W. Meyer-Klaucke, M. Koker, J. Clos, D. Georgieva, N. Genov, H. Echner, H. Kalbacher, M. Perbandt, R. Bredehorst, W. Voelter and Ch. Betzel. Comparative analysis of the human and chicken PrP copper binding region at pH 6.5. J. Biol. Chem. 280:13987-13992 (2005)

M. Perbandt, J. Höppner, Ch. Betzel, R.D. Walter and E. Liebau. Structure of the major cytosolic glutathione S-transferase from the parasitic nematode Onchocerca volvulus. J. Biol. Chem. 280:12630-12636 (2005)

N. Singh, T. Jabeen, S. Sharma, I. Roy, M.N. Gupta, S. Bilgrami, R. K. Somvanshi, S. Dey, M. Perbandt, Ch. Betzel, A. Srinivasan and T.P. Singh. Detection of native peptides as potent inhibitors of enzymes. FEBS Letters 272:562-572 (2005)

2004

D. Georgieva, W. Rypniewski, H. Echner, M. Perbandt, M. Koker, C. Clos, L. Redecke, R. Bredehorst, W. Voelter, N. Genov and Ch. Betzel. Synthetic human prion protein octapeptide repeat binds to the proteinase K active site. Biochem. Biophys. Res. Commun. 325:1406-1411 (2004)

D. Georgieva, M. Koker, L. Redecke, M. Perbandt, J. Clos, R. Bredehorst, N. Genov and Ch. Betzel. Oligomerization of the proteolytic products is an intrinsic property of prion proteins. Optimization of the prion proteolysis. Biochem. Biophys. Res. Commun. 323:1278-1286 (2004)

J Höppner, M. Perbandt, Ch. Betzel, R.D. Walter and E. Liebau. Crystallization of the major cytosolic glutathione S-transferase from Onchocerca volvulus. Acta Crystallogr. D Biol. Crystallogr. 60:1496-1497 (2004)

D.Georgieva, N. Genov, M. Perbandt, W. Voelter and Ch. Betzel. Contribution of Disulfide Bonds and Calcium to the Molluscan Hemycyanin Stability. Zeitschrift f. Naturforschung Sec. C. 59:281-287 (2004)

D. Georgieva, M. Perbandt, W.R. Rypniewski, K. Hristov, N. Genov and Ch. Betzel. The X-ray structure of a snake venom Gln48 phospholipase A2 at 1.9 Å resolution reveals anion-binding sites. Biochem. Biophys. Res. Commun. 316:33-38 (2004)

M. Perbandt, C. Burmeister, R.D. Walter, C. Betzel and E. Liebau. Native and inhibited structure of a MU-class related glutathione S-transferase from Plasmodium falciparum. J. Biol. Chem. 279:1336-1342 (2004)

M. Vallazza, M. Perbandt, S. Klussmann, W. Rypniewski, H.M. Einspahr, V.A. Erdmann, C. Betzel. First look at RNA in L-configuration. Acta Crystallogr. D Biol. Crystallogr. 60:1-7 (2004)

2003

M. Perbandt, I.H. Tsai, A. Fuchs, S. Banumathi, K.R. Rajashankar, I. Tsai, D, Georgieva, N. Kalkura, T.P. Singh, N. Genov, C. Betzel. Crystal Structure of the Hetereodimeric Neurotoxic Complex Daboiatoxin F (RV-4/RV-7) from the Venom of Daboia ruselli formosensis (Taiwan Viper) at 1.9 Å. Acta Crystallogr. D Biol. Crystallogr. 59:1679-1687 (2003)

D. Georgieva, W.R. Rypniewski, M. Perbandt, M. Jain, N.Genov and Ch Betzel. Crystallization and preliminary X-ray diffraction studies of a toxic phospholipase A2 from the venom of Vipera ammodytes meridionalis complexed to a synthetic inhibitor. Biochim. Biophys. Acta  1650:1-3 (2003)

C. Burmeister, M. Perbandt, C. Betzel, R.D. Walter and E. Liebau. Crystallization of the glutathione S-transferase from Plasmodium falciparum. Acta Crystallogr. D Biol. Crystallogr. 59:1650-1652 (2003)

M. Perbandt, E. Guthöhrlein, W.R. Rypniewski, K. Idakieva, S. Stoeva, W. Voelter, N. Genov and Ch. Betzel. The Structure of a Functional Unit from the Wall of a Gastropod Hemocyanin Offers a Possible Mechanism for Cooperativity. Biochemistry, 42(21), 6341-6346 (2003)

M. Perbandt, M. Barciszewska, C. Betzel, V.A. Erdmann & J. Barciszewski. A critical role in the specific cleavage of the anticodon loop of some eukaryotic methionine initiator tRNAs. Mol. Biol. Reports 30:27-31 (2003)

2002

V. Chandra, J. Jasti, P. Kaur, S. Dey, M. Perbandt, A. Srinivasan, C. Betzel & T.P. Singh. Design of specific peptides as inhibitors of phospholipase A2: crystal structure of a complex formed between phospholipase A2 and a designed peptide Phe-Leu-Ser-Tyr-Lys at 1.8 Å resolution. J. Biol. Chem. 277:41079-41085 (2002)

S. Shlyapnikov, V. Lunin, E.V. Blagova, L.V. Abaturov, M. Perbandt, Ch. Betzel and A.M. Mikhailov A Comprarative Structure-Function Analysis and Molecular Mechanism of Action from Serratia Marcescens and Physarium polycephalum. Russian J. of Bioorg. Chem. 38:20-27 (2002)

C. Nötzel, V. Chandra, M. Perbandt, K.R. Rajashankar, T.P. Singh, B. Aleksiev, N. Kalkura, N. Genov & Ch. Betzel. Enzymatic Activity and Inhibition of the neurotoxic complex Vipoxin from the Venom of Vipera ammodytes meridionalis. Z. Naturforsch. 57c:1078-1083 (2002)

M. Vallazza, S. Banumathi, M. Perbandt, K. Moore, L. deLucas, C. Betzel & V.A. Erdmann. Crystallization and structure of Thermus flavus 5S rRNA helix B. Acta Crystallogr. D Biol. Crystallogr. 58:1700-1703 (2002)

2001

S.V. Shliapnikov, V.V. Lunin, E.V. Blagova, M. Perbandt, Ch. Betzel and A. Mikhailov X-ray structural analysis of magnesium-containing Serratia marcescens endonuclease. Bioorg Khim. 27:417-425 (2001)

C. Betzel, S. Gourinath. P. Kumar, P. Kaur, M. Perbandt, S. Eschenburg and T.P. Singh. Structure of a serine protease Proteinase K from Tritirachium album limber at 0.98 Å resolution. Biochemistry 40:3080-3088 (2001)

M. Perbandt, V. Chandra, K.R. Rajashankar, K. Idakieva, K. Parvanova, W. Rypniewski, S. Stoeva. W. Voelter, N. Genov and Ch. Betzel. Crystallization and preliminary studies of the external functional unit RtH2-e from Rapana thomasiana. Acta Crystallogr. D Biol. Crystallogr. 57:1663-1665 (2001)

M. Perbandt, V. Chandra, K. Idakieva, K. Parvanova, W. Rypniewski, N. Genov, S. Stoeva. W. Voelter and Ch. Betzel. Crystallization, Preliminary X-ray Analysis and Amino Acid Sequence Studies of External Functional Unit from the Rapana thomasiana Grosse (Mollusc, Gastropod) Hemocyanin. J. Cryst. Growth 232:353-360 (2001)

M. Perbandt, M. Vallazza, C. Lippmann, Ch. Betzel and V. A. Erdmann. Crystal structure of an RNA duplex with an unusual GC pair in wobble-like conformation at 1.6 Å resolution. Acta Crystallogr. D Biol. Crystallogr. 57:219-224 (2001)

M. Vallazza, A. Senge, C. Lippmann, M. Perbandt, Ch. Betzel, R. Bald and V.A. Erdmann. Crystallization and X-ray diffraction data of Thermus flavus 5S rRNA helices. J. Cryst. Growth 232:340-352 (2001)

2000

S.S. Funari, G. Rapp, M. Perbandt, M. Vallazza, V.A. Erdmann, Ch. Betzel, D. Svergun. Structure of free Thermus flavus 5S rRNA at 1.3 nm resolution from synchrotron X-ray solution scattering. J. Biol. Chem. 40:31283-31288 (2000)

S.V. Shlyapnikov, V.V. Lunin, M. Perbandt, K.M. Polyakov, V.Yu. Lunin, V.M. Levdikov, Ch. Betzel and A.M. Mikhailov. Atomic structure of the Serratia marcescens-endonuclease at 1.1 Å resolution and the enzyme reaction mechanism. Acta Crystallogr. D Biol. Crystallogr. 56:567-572 (2000)

S. Lorenz, M. Perbandt, Lippmann, C., Moore, K., DeLucas, L.J., Ch. Betzel and V. A. Erdmann. Crystallization of engineered Thermus flavus 5S rRNA under earth and microgravity conditions. Acta Crystallogr. D Biol. Crystallogr. 56:498-500 (2000)

1999

S.V. Shlyapnikov, E.V. Blagova, V.M. Levdikov, V.Yu. Lunin, V.V. Lunin, A.M. Mikhailov, Ch. Betzel, K.R. Rajashankar and M. Perbandt. The Extracellular Endonuclease of Serratia marcescens. II. Actice Site Amino Acid Residues and Hypothetical Mechanism of Enzyme Function. Mol. Biol. 33:398-404 (1999)

V.Y. Lunin, E.V. Blagova, V.M. Levdikov, V.V. Lunin, S.V. Shlyapnikov, M. Perbandt, K.R. Rajashankar, Ch. Betzel and A.M. Mikhailov. Extracellular Endonuclease of Serratia marcescens. First Three-Dimensional Structure of crystalline Protein at 1.7 Å. Mol. Biol. 33:180-187 (1999)

R. Krauspenhaar, S. Eschenburg, M. Perbandt, V. Kornilov, N. Konareva, I. Mikailova, S. Stoeva, R. Wacker, T. Maier, T. Singh, A. Mikhailov, W. Voelter and Ch. Betzel. Crystal Structure of Mistletoe Lectin I from Viscum album. Biochem. Biophys. Res. Commun. 257:418-424 (1999)

1998

Ch. Zoerb, K. Brunner, M. Perbandt, Ch. Betzel and G. Wagner. Cloning, Recombinant Expression and Characterization of Wild-Type-105-Trp-Calmodulin of the Green Alga Mougeotia scalaris. Bot. Acta 111:346-353 (1998)

M. Perbandt, A. Nolte, S. Lorenz, R. Bald, Ch. Betzel and V. A. Erdmann. Crystal structure of domain E of Thermus flavus 5S rRNA: a helical RNA structure including a hairpin loop. FEBS Lett. 429:211-215 (1998)

1997

M. Perbandt, J. Wilson, S. Eschenburg, I. Mancheva, B. Aleksiev, N. Genov, P. Willingmann, W. Weber, T. Singh and Ch. Betzel. Crystal structure of vipoxin at 2.0 Å: an example of regulation of a toxic function generated by molecular evolution. FEBS Lett. 412:573-577 (1997)

1996

A. Bufe, Ch. Betzel, G. Schramm, A. Petersen, W. Becker, M. Schlaak, M. Perbandt, Z. Dauter and W. Weber. Crystallization and Preliminary Diffraction Data of a Major Pollen Allergen. J. Biol. Chem. 271:27193-27196 (1996)