Research - Centre for Biotechnology

Research > Research areas > Protein Crystallography

Protein Crystallography

Group Leader

Tassos Papageorgiou, PhD
Adjunct Professor in Biochemistry and Structural Biology
Group leader
tassos.papageorgiou [at] btk.fi

Contact Information

Phone: +358 2 333 8012
FAX: +358 2 333 8000
Mailing address: Turku Centre for Biotechnology,
Biocity Turku, 5th floor, Tykistokatu 6, Turku 20521
Finland

Projects

We use X-ray crystallography as the major tool to provide detailed information on the structure and function of biological molecules. Knowledge of the 3-dimensional structure of proteins is essential to understand at the atomic level how proteins functions or, in the case of diseases, how a protein malfunctions. Our current projects include:

Pathogen-host interactions. The complexity of pathogen-host interactions is investigated in our group by looking at proteins involved in stress protection. Understanding the mechanistic details of bacterial survival under various forms of stress could be useful in the design of novel ways to combat or prevent disease. Peroxide resistance, for example, plays a major role in the survival of bacteria and the spread of disease. We are particularly interested in a class of ferritin-like proteins that are able to bind and oxidize iron. By combining site-directed mutagenesis, protein structure determination and X-ray absorption spectroscopy we aim to provide a more comprehensive view of the role and function of ferritin-like proteins in bacterial survival.

Signalling proteins. Signalling is a biological process that depends strongly on molecular recognition and protein-protein interactions. Our aim is to understand the structural aspects of this process at atomic level and to use the obtained structural information for the development of novel ways of therapeutic intervention in disease.

Enzyme stability and function. Understanding enzyme adaptation in extreme environmental conditions will enable the design of better performance tailor-made enzymes in biotechnology. Structure determination at high/atomic resolution combined with thermal denaturation analysis and other biophysical techniques is expected to give a better picture of the studied proteins/enzymes under various conditions. Thus, for protein stability studies we use a multidisciplinary approach that includes, apart from X-ray crystallography, several biophysical methods such as fluorescence spectroscopy, microcalorimetry and circular dichroism, and enzyme kinetic assays.

Radiation damage. The use of synchrotron radiation has been central to all our structural studies. By analyzing data collected in synchrotrons followed by close inspection of the resultant protein structures at atomic resolution we have been able to study more fundamental problems in crystallography, such as radiation damage. The latter arises from the interaction of powerful X-rays with biological specimens and has become a critical issue in modern data collection strategies. Understanding this process and finding ways to prevent it is important for the elucidation of more accurate protein structures.

An example of a typical day in our group is shown here

A star is born...here

At ease...here

Our crystallography core facility pages can be found here

Selected Publications

Chronopoulou, E.G, Papageorgiou, A.C. & Labrou, N.E. (2012). Inhibition of human glutathione transferases by pesticides: Development of a simple analytical assay for the quantification of pesticides in water. J. Mol. Catal. B (in press)
Skopelitou, K., Dhavala, P., Papageorgiou, A.C. & Labrou, N.E. (2012). A glutathione transferase from Agrobacterium tumefaciens reveals a novel class of bacterial GST superfamily. PLoS One 7(4): e34263 Pubmed
Skopelitou, K., Muleta, A.W, Pavli, O., Skaracis, G.N, Flemetakis, E., Papageorgiou, A.C. & Labrou, N.E. (2012). Overlapping protective roles for glutathione transferase gene family members in chemical and oxidative stress response in Agrobacterium tumefaciens. Funct. Integr. Genomics 12: 157-172 Pubmed
Li, D.-C., Li, A.-N. & Papageorgiou, A.C. (2011) Cellulases from thermophilic fungi: Recent insights and biotechnological potential. Enzyme Res. Vol 2011, Article ID 308730 Pubmed
Haikarainen, T., Paturi, P., Lindén, J., Haataja, S., Meyer-Klaucke, W., Finne, J. & Papageorgiou, A.C. (2011). Magnetic properties and structural characterization of iron oxide nanoparticles formed by Streptococcus suis Dpr and four mutants. J. Biol. Inorg. Chem. 16: 799-807 Pubmed
Haikarainen, T., Thanassoulas, A., Stavros, P., Nounesis, G., Haataja, S.& Papageorgiou, A.C. (2011). Structural and thermodynamic characterization of metal ion binding in Streptococcus suis Dpr. J. Mol. Biol 405: 448-460 [Pubmed]
Wakadkar, S., Zhang, L.-Q., Li, D.-C., Haikarainen, T., Dhavala, P. & Papageorgiou, A.C. (2010). Expression, purification and crystallization of Chaetomium thermophilum Cu,Zn superoxide dismutase. Acta Cryst F 66(Pt 9): 1089-1092 [Pubmed ]
Haikarainen, T., Tsou, C.C.; Wu, J.J. & Papageorgiou, A.C. (2010). Structural characterization and biological implications of di-zinc binding in the ferroxidase center of Streptococcus pyogenes Dpr. Biochem. Biophys. Res. Comm. 398: 361-365 ]Pubmed ]
Wakadkar, S., Hermawan, S., Jendrossek, D. & Papageorgiou, A.C. (2010). The crystal structure of PhaZ7 at atomic (1.2 Å) resolution reveals details of the active site and suggests a substrate binding mode. Acta Cryst. F 66: 648-654.
Labrou, N.E., Papageorgiou, AC. & Avramis, V.I. (2010) Structure-function relationships and clinical applications of L-asparaginases. Curr. Med. Chem. 17: 2183-2195.
Axarli, I., Georgiadou, C., Dhavala, P., Papageorgiou, A.C. & Labrou, N.E. (2010). Investigation of the role of conserved residues Ser13, Asn48 and Pro49 in the catalytic mechanism of the tau class glutathione transferase from Glycine max. Biochim. Biophys. Acta 1804: 662-667. [Link]
Haikarainen, T. & Papageorgiou, A.C. (2010). Dps-like proteins: Structural and functional insights into a versatile protein family. Cell. Mol. Life Sci. 67, 341-351. [Link]
Haikarainen, T., Tsou, C.C., Wu, J.J. & Papageorgiou, A.C. (2010). Crystal structures of Streptococcus pyogenes Dpr reveal a dodecameric iron-binding protein with a ferroxidase site. J. Biol. Inorg. Chem. 15: 183-194.
Melissis, S.C, Papageorgiou, A.C., Labrou, N.E. & Clonis, Y.D. (2010).Purification of moloney murine leukemia virus reverse transcriptase lacking RNase activity (M-MLVH-RT) on a 9-aminoethyladenine-[1,6-diamine-hexane]-triazine selected from a combinatorial library of dNTP-mimetic ligands. J. Chromatogr. Sci. 48: 496-502.
Dhavala, P. & Papageorgiou, A.C. (2009). The crystal structure of Helicobacter pylori L-asparaginase at 1.4 Å resolution. Acta Crystallogr. D 65, 1253-1261.
Mitsiki, E., Papageorgiou, A. C., Iyer, S., Thiyagarajan, N., Prior, S. H., Sleep, D., Finnis, C. & Acharya, K. R. (2009). Structures of native human thymidine phosphorylase and in complex with 5-iodouracil. Biochem. Biophys. Res. Commun. 386: 666-670.
Axarli, I. Dhavala, P., Papageorgiou, A.C. & Labrou, N.E. (2009). Crystal structrure of Glycine max glutathione transferase in complex with glutathione: investigation of the induced-fit mechanism operating by the tau class glutathione transferases. Biochem. J. 422: 247-256.
Axarli, I. Dhavala, P., Papageorgiou, A.C. & Labrou, N.E. (2009). Crystallographic and functional characterization of the fluorodifen-inducible glutathione transferase from Glycine max reveals an active site topography suited for diphenylether herbicides and a novel L-site. J. Mol. Biol. 385: 984-1002 [Link]
Papageorgiou, A.C, Hermawan, S., Singh C.B & Jendrossek, D. (2008) Structural basis of poly(3-hydroxybutyrate) hydrolysis by PhaZ7 depolymerase from Paucimonas lemoignei. J. Mol. Biol. 382: 1184-1194 [Link]
Dhavala, P., Krasotkina, J., Dubreuil, C. & Papageorgiou, A.C. (2008) Expression, purification and crystallisation of Helicobacter pylori L-asparaginase. Acta Crystallogr. F 64: 740-742 [Link]
Papageorgiou, A.C., Posypanova, G., Andersson, C., Sokolov, N. & Krasotkina, J. (2008). Structural and functional insights into Erwinia carotovora L-asparaginase. FEBS J. 275: 4306-4316 [Link]
Havukainen, H., Haataja, S., Kauko, A., Pulliainen, A.T., Salminen, A., Haikarainen, T., Finne, J. & Papageorgiou, A.C. (2008). Structural basis of zinc- and terbium-mediated inhibition of ferroxidase activity in Dps ferritin-like proteins. Protein Sci. 17: 1513-1521 [Link]
SaarinenS., Kato, H., Uchiyama, T., Miyoshi-Akiyama, T. & Papageorgiou, A.C. (2007). Crystal structure of Streptococcus dysgalactiae-derived mitogen reveals a zinc-binding site and alterations in TcR binding. J. Mol. Biol. 373: 1089-1096 [Link]
Weckstrom, K. & Papageorgiou, A.C. (2007). Lower consolute boundaries of the nonionic surfactant C8E5 in aqueous alkali halide solutions. An approach to reproduce the effects of alkali halides on the cloud-point temperature. J. Coll. Interf. Sci. 310: 151-162
Zhao, J., Hayashi, T., Saarinen, S., Papageorgiou, A.C., Kato, H., Imanishi, K., Kirikae, T., Abe, R., Uchiyama, T. & Miyoshi-Akiyama, T. (2007). Cloning, expression and characterization of the superantigen streptococcal pyrogenic exotoxin-G from Streptococcus dysgalactiae. Infect. Immun. 75: 1721-1729
Kauko, A., Pulliainen, A.T., Haataja, S., Meyer-Klaucke, W., Finne, J. & Papageorgiou, A.C. (2006). Iron incorporation in Streptococcus suis Dps-like peroxide resistance protein Dpr requires mobility in the ferroxidase center and leads to the formation of a ferrihydrite-like core. J. Mol. Biol. 364: 97-109. [Link]
Papageorgiou, A.C, Saarinen, S., Ramirez-Bartutis, R., Kato, H., Uchiyama, T., Kirikae, T. & Miyoshi-Akiyama, T. (2006). Expression, purification and crystallisation of Streptococcus dysgalactiae-derived mitogen. Acta Crystallogr. F. 62: 242-244
Kapetaniou, E.G., Thanassoulas, A., Dubnovitsky, A.P., Nounesis, G. & Papageorgiou, A.C. (2006). The effect of pH on the structure and stability of Bacillus circulans ssp. alkalophilus phosphoserine aminotransferase: Thermodynamic and crystallographic studies. Proteins 63: 742-753 [Link]
Pulliainen, A.T., Kauko, A., Haataja, S., Papageorgiou, A.C. & Finne, J. (2005). Dps/Dpr ferritin-like protein: Insights into the mechanism of iron incorporation and evidence for a central role in cellular iron homeostasis. Mol. Microbiol. 57: 1086-1100. [Link]
Kapetaniou, E.G, Braaz, R., Jendrossek, D. & Papageorgiou, A.C. (2005). Crystallization and preliminary X-ray analysis of a novel thermoalkalophilic depolymerase (PhaZ7) from Paucimonas lemoignei. Acta Crystallogr. F61: 479-481.
Wikman, L.E.K., Krasotkina, J., Kuchumova, A., Sokolov, N.N. & Papageorgiou, A.C. (2005). Crystallization and preliminary crystallographic analysis of L-asparaginase from Erwinia carotovora. Acta Crystallogr. F61: 407-409.
Dubnovitsky,. A.P., Ravelli, R.B.G., Popov, A.N. & Papageorgiou, A.C. (2005). Strain relief at the active site of phosphoserine aminotransferase induced by radiation damage. Protein Sci. 14: 1498-1507. [Link]
Mialon A., Sankinen, M., Söderström, H., Junttila, T.T., Holmström, T., Koivusalo, R., Papageorgiou, A.C., Johnson, R.S., Hietanen, S., Elenius, K. & Westermarck, J. (2005). DNA topoisomerase I is a co-factor for c-Jun in the regulation of EGFR expression and cancer cell proliferation. Mol. Cell. Biol. 25: 5040-5051.
Dubnovitsky, A.P., Kapetaniou, E.G. & Papageorgiou, A.C. (2005). Enzyme adaptation to alkaline pH: Atomic resolution (1.08 Å) structure of phosphoserine aminotransferase from Bacillus alkalophilus. Protein Sci. 14: 97-110.
Papageorgiou, A.C. & Wikman, L. (2004). Is JAK3 a new drug target in immunomodulation-based therapies? Trends Pharmacol. Sci. 25: 558-562
Kauko, A., Haataja, S., Pulliainen, A.T., Finne, J. & Papageorgiou, A.C. (2004). Crystal structure of Streptococcus suis Dps-like peroxide resistance protein Dpr: Implications for iron incorporation. J. Mol. Biol. 338: 547-558
Papageorgiou, A.C., Baker, M.D., McLeod, J.D., Goda, S., Manzotti, C.N., Sansom, D.M., Tranter, H.S. & Acharya, K.R. (2004). Identification of a secondary zinc-binding site in staphylococcal enterotoxin C2: Implications for superantigen recognition. J. Biol. Chem 279: 1297-1303
Dubnovitsky, A.P., Kapetaniou, E.G., & Papageorgiou, A.C. (2003). Expression, purification, crystallisation and preliminary crystallographic analysis of phosphoserine aminotransferase from Bacillus alcalophilus. Acta Crystallogr. D59: 2319-2321.
Hirvonen, M. & Papageorgiou, A.C. (2003). Crystal structure of a family 45 endoglucanase from Melanocarpus albomyces: Mechanistic implications based on the free and cellobiose-bound forms. J. Mol. Biol. 329: 403-410
Chavali, G., Papageorgiou, A.C., Olson, K.A., Fett, J.W., Hu, G.-F., Shapiro, R.& Acharya K.R. (2003). Crystal structure of an angiogenic molecule, human angiogenin, in complex with the Fab fragment of its neutralising monoclonal antibody 26-2F at 2.0 Å resolution. Structure 11: 875-885
Swaminathan, G.W, Holloway, D., Colvin, R.A., Campanella, G.K., Papageorgiou, A.C., Luster, A.D. & Acharya, K.R. (2003). Crystal structures of oligomeric forms of the IP10/CXCL10 chemokine. Structure 11: 521-532
Gordon, K., Redelinghuys, P., Schwager, S.L.U., Ehlers, M.R.W., Papageorgiou, A.C., Natesh, R., Acharya, K.R. & Sturrock, E.D. (2003). Deglycosylation, processing, and crystallisation of human testis angiotensin-converting enzyme. Biochem. J. 371: 437-442
Haataja. S., Penttinen, A., Pulliainen, A.T., Tikkanen, K., Finne, J. & Papageorgiou, A.C. (2002). Expression, purification and crystallisation of Dpr, a ferritin-like protein from the gram-positive meningitis-associated bacterium Streptococcus suis. Acta Crystallogr. D58: 1851-1853
Hirvonen, M. & Papageorgiou, A.C. (2002). Crystallisation and preliminary crystallographic analysis of a family 45 endoglucanase from the thermophilic fungus Melanocarpus albomyces. Acta Crystallogr. D58, 336-338
Baker, M.D., Papageorgiou, A.C., Titball, R.W., Miller, J., White, S., Lingard, B., Lee, J.-J., Cavanagh, D., Kehoe, M.A., Robinson, J.H. & Acharya, K.R.. (2002). Structural and functional role of Threonine-112 in a superantigen Staphylococcus aureus enterotoxin-B. J. Biol. Chem. 277: 2756-2762
Greene, L.H., Chrysina, E.D., Irons, L.I., Papageorgiou, A.C., Acharya, K.R. & Brew, K. (2001). Role of conserved residues in structure and stability: Tryptophans of human serum retinol-binding protein, a model for the lipocalin superfamily. Protein Sci. 10: 2301-2316
Baker, M., Gutman, D.M., Papageorgiou, A.C., Collins, C.M. & Acharya, K.R. (2001). Structural features of a zinc binding site in superantigen streptococcal pyrogenic exotoxin A (SpeA1): Implications for MHC class II recognition. Protein Sci. 10: 1268-1273
Papageorgiou, A.C. & Acharya, K.R. (2000). Microbial superantigens: From structure to function. Trends Microbiol. 8: 369-375.
Papageorgiou, A.C., Plano, L.R.W, Collins, C.M & Acharya, K.R (2000). Structural similarities and differences in Staphylococcus aureus exfoliative toxins A and B as revealed by their crystal structures. Protein Sci. 9: 610-618.
Papageorgiou, A. C., Collins, C. M., Gutman, D. M., Kline, J. B., O'Brien, S. M., Tranter, H. S. & Acharya, K. R. (1999). Structural basis for the recognition of superantigen streptococcal pyrogenic exotoxin A (SpeA1) by MHC class II molecules and T-cell receptors. EMBO J. 18: 9-21.