Schonbrunn

Associate Professor

Associate Member, Drug Discovery Department
Scientific Director, Structural Biology Core
Associate Professor, University of South Florida, Oncologic Sciences

Phone: 813-745-4703
Email: ernst.schonbrunn@moffitt.org


Education:

PhD - Max-Planck Research Unit for Structural Molecular Biology, Hamburg, Germany, 1991 (Biology/Protein Crystallography)

Postdoctoral

Fellowship - Max-Planck Research Unit for Structural Molecular Biology, Hamburg, Germany, 1996 (Protein Crystallography)

Publications

  • Olesen SH, Ingles DJ, Zhu JY, Martin MP, Betzi S, Georg GI, Tash JS, Schonbrunn E. Stability of the Human Hsp-90p50cdc37 Chaperone Complex against Nucleotides and Hsp90 Inhibitors, and the influence of Phosphorolaytion by Casein Kinase 2. Journal Molecules, 2015. Pubmed ID: 25608045
  • Mishra MK, Urick AK, Ember SW, Schönbrunn E, Pomerantz WC. Fluorinated Aromatic Amino Acids Are Sensitive 19F NMR Probes for Bromodomain-Ligand Interactions. 2014. Pubmed ID: 25290579
  • Ember SW, Zhu JY, Olesen SH, Martin MP, Beckker A, Berndt N, Georg GI, Schönbrunn E. Acetyl-lysine binding site of bromodomain-containing protein 4 (BRD4) interacts with diverse kinase inhibitors. 2014. PubMed ID: 24568369
  • Shigetomi K, Olesen SH, Yang Y, Mitsuhashi S, Schönbrunn E, Ubukata M. MurA as a Primary Target of Tulipalin B and 6-Tuliposide B. Biosci Biotechnol Biochem. 2013. PubMed ID: 24317075
  • Martin MP, Olesen SH, Georg GI, Schönbrunn E. Cyclin-dependent kinase inhibitor dinaciclib interacts with the acetyl-lysine recognition site of bromodomains. ACS Chem Biol. 2013 Nov 15;8(11):2360-5. doi: 10.1021/cb4003283. 2013. PubMed ID: 24007471
  • Schonbrunn E, Betzi S, Alam R, Martin MP, Becker A, Han H, Francis R, Chakrasali R, Jakkaraj S, Kazi A, Sebti SM, Cubitt CL, Gebhard AW, Hazlehurst LA, Tash JS, Georg GI. Development of highly potent and selective diaminothiazole inhibitors of cyclin-dependent kinases. J Med Chem. 2013. PubMed ID: 23600925
  • Olesen SH, Ingles DJ, Yang Y, Schönbrunn E. Differential antibacterial properties of the MurA inhibitors terreic acid and fosfomycin. J Basic Microbiol. 2013. PubMed ID: 23686727
  • Wu S, Chen L, Becker A, Schonbrunn E, Chen J. Casein kinase 1α regulates an MDMX intramolecular interaction to stimulate p53 binding. Mol Cell Biol. 2012. PubMed ID: 23028042
  • Patel RA, Forinash KD, Pireddu R, Sun Y, Sun N, Martin MP, Schönbrunn E, Lawrence NJ, Sebti SM. RKI-1447 is a potent inhibitor of the Rho-associated ROCK kinases with anti-invasive and antitumor activities in breast cancer. Cancer Res. 2012. PubMed ID: 22846914
  • Martin MP, Alam R, Betzi S, Ingles DJ, Zhu JY, Schönbrunn E. A novel approach to the discovery of small-molecule ligands of CDK2. Chembiochem. 2012. PubMed ID: 22893598
  • Lawrence HR, Martin MP, Luo Y, Pireddu R, Yang H, Gevariya H, Ozcan S, Zhu JY, Kendig R, Rodriguez M, Elias R, Cheng JQ, Sebti SM, Schonbrunn E, Lawrence NJ. Development of o-chlorophenyl substituted pyrimidines as exceptionally potent aurora kinase inhibitors. J Med Chem. 2012. PubMed PMID: 22803810
  • Pireddu R, Forinash KD, Sun NN, Martin MP, Sung SS, Alexander B, Zhu JY, Guida WC, Schönbrunn E, Sebti SM, Lawrence NJ. Pyridylthiazole-based ureas as inhibitors of Rho associated protein kinases (ROCK1 and 2). Medchemcomm. 2012. PubMed PMID: 23275831
  • Martin MP, Zhu JY, Lawrence HR, Pireddu R, Luo Y, Alam R, Ozcan S, Sebti SM, Lawrence NJ, Schönbrunn E. A novel mechanism by which small molecule inhibitors induce the DFG flip in Aurora A. ACS Chem Biol. 2012. PubMed PMID: 22248356
  • Zhu JY, Yang Y, Han H, Betzi S, Olesen SH, Marsilio F, Schönbrunn E. Functional consequence of covalent reaction of phosphoenolpyruvate with UDP-N-acetylglucosamine 1-carboxyvinyltransferase (MurA). J Biol Chem. 2012. PubMed PMID: 22378791
  • Lee JC, Francis S, Dutta D, Gupta V, Yang Y, Zhu JY, Tash JS, Schönbrunn E, Georg GI. Synthesis and evaluation of eight- and four-membered iminosugar analogues as inhibitors of testicular ceramide-specific glucosyltransferase, testicular β-glucosidase 2, and other glycosidases. J Org Chem. 2012. PubMed PMID: 22432895
  • Doi K, Li R, Sung SS, Wu H, Liu Y, Manieri W, Krishnegowda G, Awwad A, Dewey A, Liu X, Amin S, Cheng C, Qin Y, Schonbrunn E, Daughdrill G, Loughran TP Jr, Sebti S, Wang HG. Discovery of marinopyrrole A (maritoclax) as a selective Mcl-1 antagonist that overcomes ABT-737 resistance by binding to and targeting Mcl-1 for proteasomal degradation. J Biol Chem. 2012. PubMed PMID: 22311987
  • Li R, Martin MP, Liu Y, Wang B, Patel RA, Zhu JY, Sun N, Pireddu R, Lawrence NJ, Li J, Haura EB, Sung SS, Guida WC, Schonbrunn E, Sebti SM. Fragment-based and structure-guided discovery and optimization of Rho kinase inhibitors. J Med Chem. 2012. PubMed PMID: 22272748
  • Pollegioni L, Schonbrunn E, Siehl D. Molecular basis of glyphosate resistance-different approaches through protein engineering. FEBS J. 2011. PubMed PMID: 21668647
  • Betzi S, Alam R, Martin M, Lubbers DJ, Han H, Jakkaraj SR, Georg GI, Schönbrunn E. Discovery of a potential allosteric ligand binding site in CDK2. ACS Chem Biol. 2011. PubMed PMID: 21291269
  • Berndt N, Yang H, Trinczek B, Betzi S, Zhang Z, Wu B, Lawrence NJ, Pellecchia M, Schönbrunn E, Cheng JQ, Sebti SM. The Akt activation inhibitor TCN-P inhibits Akt phosphorylation by binding to the PH domain of Akt and blocking its recruitment to the plasma membrane. Cell Death Differ. 2010 May 21. Pubmed ID: 20489726
  • Han H, Yang Y, Olesen SH, Becker A, Betzi S, Schönbrunn E. The Fungal Product Terreic Acid is a Covalent Inhibitor of the Bacterial Cell Wall Biosynthetic Enzyme UDP-N-acetylglucosamine 1-carboxyvinyltransferase (MurA) (2010). Biochemistry. 49:4276-82 Pubmed ID: 20392080
  • Mahajan K, Coppola D, Challa S, Fang B, Chen YA, Zhu W, Lopez AS, Koomen J, Engelman RW, Rivera C, Muraoka-Cook RS, Cheng JQ, Schönbrunn E, Sebti SM, Earp HS, Mahajan NP (2010). Ack1 Mediated AKT/PKB Tyrosine 176 Phosphorylation Regulates Its Activation. PLoS One 5:e9646. Pubmed ID: 20333297
  • Phan J, Li Z, Kasprzak A, Li B, Sebti S, Guida W, Schönbrunn E, Chen J. Structure-based design of high affinity peptides inhibiting the interaction of p53 with MDM2 and MDMX. J Biol Chem. 2010 Jan 15;285(3):2174-83. Pubmed ID: 19910468
  • Funke T, Yang Y, Han H, Healy-Fried M, Olesen S, Becker A, Schönbrunn E. Structural basis of glyphosate resistance resulting from the double mutation Thr97 -> Ile and Pro101 -> Ser in 5-enolpyruvylshikimate-3-phosphate synthase from Escherichia coli. J Biol Chem. 2009 Apr 10;284(15):9854-60. Pubmed ID: 19211556
  • Alontaga AY, Rodriguez JC, Schönbrunn E, Becker A, Funke T, Yukl ET, Hayashi T, Stobaugh J, Moënne-Loccoz P, Rivera M. Structural characterization of the hemophore HasAp from Pseudomonas aeruginosa: NMR spectroscopy reveals protein-protein interactions between Holo-HasAp and hemoglobin. Biochemistry. 2009 Jan 13;48(1):96-109. Pubmed ID: 19072037
  • Wang A, Rodríguez JC, Han H, Schönbrunn E, Rivera M. X-ray crystallographic and solution state nuclear magnetic resonance spectroscopic investigations of NADP+ binding to ferredoxin NADP reductase from Pseudomonas aeruginosa. Biochemistry. 2008 Aug 5;47(31):8080-93. Pubmed ID: 18605699
  • Funke T, Healy-Fried M, Han H, Alberg D, Bartlett P, Schonbrunn E. Differential Inhibition of Class I and Class II5-Enolpyruvylshikimate-3-phosphate Synthases by Tetrahedral Reaction Intermediate Analogues. Biochemistry. 2007 Nov 20;46(46):13344-13351. Pubmed ID: 17958399
  • Healy-Fried M, Funke T, Priestman M, Han H, Schonbrunn E. Structural basis of glyphosate tolerance resulting from mutations of Pro101 in Escherichia coli 5-enolpyruvylshikimate-3-phosphate synthase. J Biol Chem. 2007 Nov 9;282(45):32949-32955. Pubmed ID: 17855366
  • Wang A, Zeng Y, Han H, Weeratunga S, Morgan B, Moenne-Loccoz P, Schonbrunn E, Rivera M. Biochemical and structural characterization of Pseudomonas aeruginosa Bfd and FPR: ferredoxin NADP+ reductase and not ferredoxin is the redox partner of heme oxygenase under iron-starvation conditions. Biochemistry. 2007 Oct 30;46(43):12198-12211. Pubmed ID: 17915950
  • Funke T, Han H, Healy-Fried M, Fischer M, Schonbrunn E. Molecular basis for the herbicide resistance of Roundup Ready crops. Proc Natl Acad Sci U S A. 2006 Aug 29;103(35):13010-13015. Pubmed ID: 16916934
  • Li Q, Hanzlik R, Weaver R, Schonbrunn E. Molecular mode of action of a covalently inhibiting peptidomimetic on the human calpain protease core. Biochemistry. 2006 Jan 24;45(3):701-708. Pubmed ID: 16411745
  • Eschenburg S, Priestman M, Abdul-Latif F, Delachaume C, Fassy F, Schonbrunn E. A novel inhibitor that suspends the induced fit mechanism of UDP-N-acetylglucosamine enolpyruvyl transferase (MurA). J Biol Chem. 2005 Apr 8;280(14):14070-14075. Pubmed ID: 15701635
  • Eschenburg S, Priestman M, Schonbrunn E. Evidence that the fosfomycin target Cys115 in UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) is essential for product release. J Biol Chem. 2005 Feb 4;280(5):3757-3763. Pubmed ID: 15531591
  • Priestman M, Funke T, Singh I, Crupper S, Schonbrunn E. 5-Enolpyruvylshikimate-3-phosphate synthase from Staphylococcus aureus isinsensitive to glyphosate. FEBS Lett. 2005 Jan 31;579(3):728-732. Pubmed ID: 15670836
  • Priestman M, Healy M, Becker A, Alberg D, Bartlett P, Lushington G, Schonbrunn E. Interaction of phosphonate analogues of the tetrahedral reaction intermediate with 5-enolpyruvylshikimate-3-phosphate synthase in atomic detail. Biochemistry. 2005 Mar 8;44(9):3241-3248. Pubmed ID: 15736934
  • Priestman M, Healy M, Funke T, Becker A, Schonbrunn E. Molecular basis for the glyphosate-insensitivity of the reaction of 5-enolpyruvylshikimate 3-phosphate synthase with shikimate. FEBS Lett. 2005 Oct 24;579(25):5773-5780. Pubmed ID: 16225867
  • Eschenburg S, Kabsch W, Healy M, Schonbrunn E. A new view of the mechanisms of UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) and 5-enolpyruvylshikimate-3-phosphate synthase (AroA) derived from X-ray structures of their tetrahedral reaction intermediate states. J Biol Chem. 2003 Dec 5;278(49):49215-49222. Pubmed ID: 13129913
  • Eschenburg S, Healy M, Priestman M, Lushington G, Schonbrunn E. How the mutation glycine96 to alanine confers glyphosate insensitivity to 5-enolpyruvyl shikimate-3-phosphate synthase from Escherichia coli. Planta. 2002 Nov;216(1):129-135. Pubmed ID: 12430021
  • Eschenburg S, Schonbrunn E. Comparative X-ray analysis of the un-liganded fosfomycin-target murA. Proteins. 2000 Aug 1;40(2):290-298. Pubmed ID: 10842342
  • Schonbrunn E, Eschenburg S, Krekel F, Luger K, Amrhein N. Role of the loop containing residue 115 in the induced-fit mechanism of the bacterial cell wall biosynthetic enzyme MurA. Biochemistry. 2000 Mar 7;39(9):2164-2173. Pubmed ID: 10694381
  • Schonbrunn E, Eschenburg S, Luger K, Kabsch W, Amrhein N. Structural basis for the interaction of the fluorescence probe 8-anilino-1-naphthalene sulfonate (ANS) with the antibiotic target MurA. Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6345-6349. Pubmed ID: 10823915
  • Schonbrunn E, Phlippen W, Trinczek B, Sack S, Eschenburg S, Mandelkow E, Mandelkow E. Crystallization of a macromolecular ring assembly of tubulin liganded with the anti-mitotic drug podophyllotoxin. J Struct Biol. 1999 Dec 15;128(2):211-215. Pubmed ID: 10600574
  • Macheroux P, Schonbrunn E, Svergun D, Volkov V, Koch M, Bornemann S, Thorneley R. Evidence for a major structural change in Escherichia coli chorismate synthase induced by flavin and substrate binding. Biochem J. 1998 Oct 15;335 ( Pt 2):319-327. Pubmed ID: 9761730
  • Schonbrunn E, Svergun D, Amrhein N, Koch M. Studies on the conformational changes in the bacterial cell wall biosynthetic enzyme UDP-N-acetylglucosamine enolpyruvyltransferase (MurA). Eur J Biochem. 1998 Apr 15;253(2):406-412. Pubmed ID: 9654090
  • Kozielski F, Sack S, Marx A, Thormahlen M, Schonbrunn E, Biou V, Thompson A, Mandelkow E, Mandelkow E. The crystal structure of dimeric kinesin and implications for microtubule-dependent motility. Cell. 1997 Dec 26;91(7):985-994. Pubmed ID: 9428521
  • Kozielski F, Schonbrunn E, Sack S, Muller J, Brady S, Mandelkow E. Crystallization and preliminary X-ray analysis of the single-headed and double-headed motor protein kinesin. J Struct Biol. 1997 Jun;119(1):28-34. Pubmed ID: 9216086
  • Sack S, Dauter Z, Wanke C, Amrhein N, Mandelkow E, Schonbrunn E. Crystallization and preliminary X-ray diffraction analysis of UDP-N-acetylglucosamine enolpyruvyltransferase of Enterobacter cloacae. J Struct Biol. 1996 Jul;117(1):73-76. Pubmed ID: 8776890
  • Schonbrunn E, Sack S, Eschenburg S, Perrakis A, Krekel F, Amrhein N, Mandelkow E. Crystal structure of UDP-N-acetylglucosamine enolpyruvyltransferase, the target of the antibiotic fosfomycin. Structure. 1996 Sep 15;4(9):1065-1075. Pubmed ID: 8805592
  • Schweers O, Schonbrunn-Hanebeck E, Marx A, Mandelkow E. Structural studies of tau protein and Alzheimer paired helical filaments show no evidence for beta-structure. J Biol Chem. 1994 Sep 30;269(39):24290-24297. Pubmed ID: 7929085
  • Schonbrunn-Hanebeck E, Laber B, Amrhein N. Slow-binding inhibition of the Escherichia coli pyruvate dehydrogenase multienzyme complex by acetylphosphinate. Biochemistry. 1990 May 22;29(20):4880-4885. Pubmed ID: 2194562