BIOTEC: Pisabarro

Structural Bioinformatics - Pisabarro

Computational approaches to protein structure-function relationships, molecular recognition, and rational design.
Our group develops computational strategies for biotechnology innovation and drug discovery. We develop and apply computational approaches to decipher protein structure-function relationships for functional genome annotation. By understanding the molecular basis of protein recognition, we can unravel protein function and its consequences in biological processes. We also use modelling and computer simulation techniques to rationally engineer proteins and to de novo design molecular scaffolds for selective disruption of protein networks.

Research

Integrative Bioinformatics for structure-based functional annotation of uncharacterized proteins and new target discovery

We are developing and applying Structural Bioinformatics and Computational Biology methods for identification and structure-based functional annotation of uncharacterized proteins

Computational studies on molecular recognition for rational engineering and de novo design

- Characterization of protein structure-function relationships and "3D fingerprinting".
- Detailed computational characterization of protein interfaces and their classification for comparative structural analysis.
- Comparative analysis and prediction of protein-protein and protein-ligand interactions.
- Engineering and rational design of proteins and ligands of therapeutical and/or biotechnological interests.

SCOWLP: A web-based database developed in our group for detailed characterization, classification and visualization of protein interfaces (www.scowlp.org)

Publications

Slabicki, M.; Theis, M.; Krastev, D.; Samsonov, S.; Mundwiller, E.; Junqueira, M.; Paszkowski-Rogacz, M.; Teyra, J.; Heninger, A-K.; Poser, I.; Prieur, F.; Truchetto, J.; Confavreux, C.; Marelli, C.; Durr, A.; Camdessanche, J. P.; Brice, A.; Shevchenko, F.; Pisabarro, M. T.; Stevanin, G.; Buchholz, F. "A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic paraplegia."
PLoS Biology (2010 in press)

Paszkowski-Rogacz, M.; Slabicki, M.; Pisabarro, M. T.; Buchholz, F. "PhenoFam - gene set enrichment analysis through protein structural information".
BMC Bioinformatics, 11:254 (2010)

Palencia A.; Camara-Artigas A.; Pisabarro M.T.; Martinez J.C.; Luque I. "The role of interfacial water molecules in proline-rich ligand recognition by the SH3 domain of Abl."
J Biol Chem. 285(4):2823-33 (2010)

Samsonov, S.A.; Salwiczek, M.; Anders, G.; Koksch, B.; Pisabarro, M. T. "Fluorine in protein environments: A QM and MD study".
J. Phys. Chem. B. 113(51)16400-8 (2009)

Samsonov, S.A.; Teyra, J.; Anders, G.; Pisabarro, M. T. "Analysis of the impact of solvent on contacts prediction in proteins".
BMC Struct. Biol., 9(1):22 (2009)

Salwiczek, M.; Samsonov, S.; Vagt, T.; Nyakatura, E.; Fleige, E.; Numata, J.; Cölfen, H.; Pisabarro, M. T.; Koksch, B. "Position Dependent Effects of Fluorinated Amino Acids on Hydrophobic Core Formation of a Heterodimeric Coiled Coil".
Chem. Eur. J., 15(31):7628-36 (2009)

Ding, L.; Paszkowski-Rogacz, M.; Nitzsche, A.; Slabicki, M.; Heninger, A-K; Kittler, R. Junqueira, M.; Shevchenko, A.; Schulz, H.; Hubner, N.; Doss, M. X.; Sachinidis, A.; Hescheler, J.; Iacone, R.; Anastassiadis, K.; Stewart, F.; Pisabarro, M. T.; Caldarelli, A.; Poser, I.; Theis, M.; Buchholz, F. "A genome-scale RNAi screen for Oct4 modulators defines a role of the Paf1 complex for embryonic stem cell identity".
Cell Stem Cell, 4(5):403-15 (2009)

Theis, M.; Slabicki, M.; Junqueira, M.; Paszkowski-Rogacz, M.; Sontheimer, J.; Kittler, R.; Heninger, A.; Kruusmaa, K.; Poser, I.; Hyman, A.; Pisabarro, M. T.; Gstaiger, M.; Aebersold, R.; Shevchenko, A.; Buchholz, F. "Comparative Profiling Identifies C13orf3 as a Novel Component of the Ska Complex Required for Mammalian Cell Division".
EMBO J., 28(10):1453-65 (2009)

Vagt, T.; Jäckel, C.; Samsonov, S.; Pisabarro, M. T.; Koksch, B. "Selection of a buried salt bridge by phage display".
Bioorg. Med. Chem. Lett., 19(14):3924-7 (2009)

Samsonov, S.; Teyra, J.; Pisabarro, M. T. "A molecular dynamics approach to study the importance of solvent in protein interactions".
PROTEINS: Structure, Function, and Bioinformatics, 73(2):515-25 (2008)

Baldauf, C.; Pisabarro, M. T. "Stable Hairpins with β-Peptides - A Route to Tackle Protein-Protein Interactions".
J. Phys. Chem. B,112(25):7581-91(2008)

Teyra, J.; Paszkowski-Rogacz, M.; Anders, G.; Pisabarro, M. T. "SCOWLP classification: Structural comparison and analysis of protein binding regions"
BMC Bioinformatics, 9:9 (2008)

Lättig, J.; Böhl, M.; Fischer, P.; Tischer, S.; Tietböhl, C.; Menschikowski, M.; Gutzeit, H. O.; Metz, P.; Pisabarro, M. T. “Mechanism of Inhibition of Human Secretory Phospholipase A2 by Flavonoids – Rationale for Lead Design”.
Journal of Computer-Aided Molecular Design, 21(8):473-83 (2007)

Scheike, J.; Baldauf, C.; Spengler, J.; Albericio, F.; Pisabarro, M. T.; Koksch, B. "Amide-to-ester substitution in coiled coils: the effect of removing hydrogen bonds on protein structure".
Angewandte Chemie, 46(41):7766-7769 (2007)

Teyra, J. and Pisabarro, M. T. "Characterization of Interfacial Solvent in Protein Complexes and Contribution of Wet Spots to the Interface Description"
PROTEINS: Structure, Function, and Bioinformatics, 67, 1087-1095 (2007)

Pisabarro, M. T.; Leung, B; Kwong, M.; Corpuz, R.; Frantz, G. D.; Chiang, N.; Vandlen, R.; Diehl, L. J.; Skelton, N.; Eaton, D.; Schmidt, K. N. “Novel Human Dendritic Cell- and Monocyte-attracting Chemokine-like Protein Identified by Fold Recognition Methods"
Journal of Immunology, 176, 2069-2073 (2006)

Teyra, J.; Doms, A.; Schroeder, M.; Pisabarro, M. T. "SCOWLP: a web-based database for detailed characterization and visualization of protein interfaces"
BMC Bioinformatics, 7:104 (2006)

Kittler, R.; Putz, G.; Pelletier, L.; Poser, I.; Heninger, A. K.; Drechsel, D.; Fischer, S.; Konstantinova, I.; Habermann, B.; Grabner, H.; Yaspo, M. L.; Himmelbauer, H.; Korn, B.; Neugebauer, K; Pisabarro, M. T.; Buchholz, F. “An endoribonuclease- prepared siRNA screen in human cells identifies genes essential for cell division”.
Nature, 432, 1036-1040 (2004)

Cobos, E. S.; Pisabarro M.T., Vega, C., Lacroix E., Serrano L.; Ruiz-Sanz, J. Martinez J. C. “A miniprotein scaffold used to assemble the PPII binding epitope recognized by SH3 domains”.
J. Mol. Biol., 342(1):355-365 (2004)

Leung, B.; Kwong, M.; Pisabarro, M. T.; Schmidt K. N. “Dendritic cell / monocyte-attracting chemokine DMC is a novel chemokine that has a potential role in homeostasis”.
Clinical and Investigative Medicine, 27(4), 2581 (2004)

Skelton N.J., Koehler M.F., Zobel K., Wong W.L., Yeh S., Pisabarro M.T., Yin J.P., Lasky L.A., Sidhu S.S. “Origins of PDZ domain ligand specificity. Structure determination and mutagenesis of the Erbin PDZ”.
J. Biol. Chem., 278(9):7645-7654 (2003)

Camenisch, G., Pisabarro M.T., Sherman, D., Kowalski, J., Nagel, M., Hass, P., Gurney, A., Bodary, S.C., Liang, X.H., Clark, K.R., Beresini, M.H., Ferrara, N., Gerber, H.P. “ANGPTL3 stimulates endothelial cell adhesion and migration via integrin αVβ3 and induces blood vessel formation in vivo”.
J. Biol. Chem., 277(19)17281-17290 (2002)

Pisabarro, M. T.; Leung, B; Kwong, M.; Corpuz, R.; Vandlen, R.; Gurney, A.; Eaton, D. L.; Schmidt K. N. “Tissue localization and selectivity for immature dendritic cells and monocytes suggest a role for a novel dendritic cell/monocyte attracting chemokine in homeostasis”.
Journal of Interferon & Cytokine Research, 22(1) 11-36 (2002)

Vucic, D., Deshayes, K., Ackerly, H., Pisabarro, M.T., Kadkhodayan, S., Fairbrother, W.J., Dixit , V.M. “SMAC negatively regulates the anti-apoptotic activity of ML-IAP”.
J. Biol. Chem., 277(14)12275-12279 (2002)

Wu Y.; Dowbenko D.; Pisabarro M. T.; Dillard-Telm L.; Koeppen H.; Lasky LA. "PTEN2, a golgi-associated testis-specific homologue of the PTEN tumor suppressor lipid phosphatase".
J. Biol. Chem., 276(24),21745-53 (2001)

Skelton, N. J.; Chen, Y. M.; Dubree, N.; Quan, C.; Jackson, D.; Cochran, A.; Zobel, K.; Deshayes, K.; Baca, M.; Pisabarro, M.T.; Lowman, H. B. "Structure- function analysis of a phage display-derived peptide that binds to insulin-like growth factor binding protein 1".
Biochemistry, 40(29), 8487-98 (2001)

Vucic, D.; Stennicke H.; Pisabarro, M.T.; Salvesen, G.; Dixit, V. M. "ML-IAP, a novel inhibitor of apoptosis that is preferentially expressed in human melanomas".
Curr. Biol., 10(21),1359-1366 (2000)

Uren, A. G.; O'Rourke, K.; Aravind, L.; Pisabarro, M.T.; Seshagiri, S.; Koonin, E. V.; Dixit, V. M. "Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma".
Mol. Cell, 6,961-967 (2000)

Gille, H.; Kowalski, J.; Yu, L.; Chen, H.; Pisabarro, M.T.; Davis-Smyth, T.; Ferrara, N. "A repressor sequence in the juxtamembrane domain of Flt-1 (VEGFR-1) constitutively inhibits vascular endothelial growth factor-dependent phosphatidylinositol 3'-kinase activation and endothelial cell migration".
EMBO J., 19(15), 4064-4073 (2000)

Fuh, G.; Pisabarro, M. T.; Li, Y.; Quan, C.; Lasky, L. A.; Sidhu, S. S. "Analysis of PDZ domain-ligand interactions using carboxy-terminal phage display".
J. Biol. Chem., 275(28), 21486-91 (2000)

Pisabarro, M. T.; Serrano, L.; Wilmanns, M. "Crystal structure of the Abl-SH3 domain complexed with a designed high-affinity peptide ligand. Implications for SH3-ligand interactions".
J. Mol. Biol., 281(3), 513-521 (1998)

Martinez, J. C.; Pisabarro, M. T., and Serrano, L. "Obligatory steps in protein folding".
Nat. Struct. Biol., 5(8), 721-729 (1998)

Wilcock, D., Pisabarro, M.T., Lopez-Hernandez, E., Serrano, L. & Coll, M. "Structure analysis of two CheY mutants: Importance of the hydrogen-bond contribution to protein stability".
Acta Crystalographica D, 54(3), 378-385 (1997)

Pisabarro, M. T. and Serrano, L. "Rational design of specific high-affinity peptide ligands for the Abl-SH3 domain".
Biochemistry, 35(33), 10634-10640 (1996)

Ortiz, A. R.; Pisabarro, M. T.; Gago, F.; Wade, R. C. "Prediction of drug binding affinities by comparative binding energy analysis".
J. Med. Chem., 38, 2681-2691 (1995)

Pisabarro, M. T.; Ortiz, A. R.; Gago, F.; Serrano, L. "Molecular modeling of the interaction of polyproline-based peptides with the abl-SH3 domain: rational modification of the interaction".
Prot. Engineering, 7 (12), 1455-1462 (1994)

Pisabarro, M. T.; Ortiz, A. R.; Serrano, L.; Wade, R. C. "Homology modeling of the abl-SH3 domain".
Proteins, 20, 203-215 (1994)

Pisabarro, M. T.; Ortiz, A. R.; Palomer, A.; Cabré, F.; García, M. L.; Wade, R. C.; Gago, F; Mauleón, D.; Carganíco, G. "Rational modification of a human synovial fluid phospholipase A2 inhibitor leading to enhanced activity".
J. Med.Chem., 37, 337-341 (1994)

Pisabarro, M. T.; Palomer, A.; Ortiz, A. R.; Wade, R. C.; Gago, F.; Mauleon, D.; Garganico, G. "Rational drug design: GRID- and LUDI-based structural modifications of a human synovial fluid phospholipase A2 inhibitor leading to enhanced activity".
J. Mol. Graphics, 12:72 (1994)

Ortiz, A. R.; Pisabarro, M. T.; Gago, F. "Molecular model of the interaction of bee venom phospholipase A2 with manoalide".
J. Med. Chem., 36 , 1866-1879 (1993)

Ortiz, A. R.; Pisabarro, M. T.; Gallego, J.; Gago, F. "Implications of a consensus recognition site for phosphatidylcholine separate from the active site in cobra venom phospholipase A2".
Biochemistry, 31 (11), 2887-96 (1992)

Funding

Klaus Tschira Stiftung

TRANSREGIO 67

Group Leader short CV

María Teresa (Mayte) Pisabarro

1997: PhD, Structural and Computational Biology, EMBL Heidelberg, Germany (Boehringer Ingelheim Fonds Fellow)
1997-1998: Postdoctoral, EMBL Heidelberg and UCSF, San Francisco, USA
1998-2002: Group Leader, Protein Engineering, Genentech Inc., San Francisco, USA
2002-2004: Visiting scientist, MPI CBG Dresden, Germany
Since 2004: Group Leader, Structural Bioinformatics, BIOTEC TU Dresden, Germany