Department of Biochemistry

Glycobiochemistry

Research team

  • RNDr. Michaela Wimmerová, Ph.D.,
  • Mgr. Nikola Kostlánová, Ph.D.,
  • Mgr. Martina Pokorná, Ph.D.
  • MSc. Monia Delia, Ph.D.
  • Mgr. Marie Pokorná
  • Ing. et Ing. Jan Adam
  • Mgr. Ondřej Šulák
  • Mgr. Lenka Malinovská
  • Mgr. Josef Houser

Web page of project

http://orion.chemi.muni.cz/michaw/research.htm

Project summary

Carbohydrates are essential for life as structural and energy storage components, and as stabilisation, recognition, signalling and communication agents. The multiple roles of carbohydrates arise from the stability and the stereochemical diversity of glycosidic bonds. The unique branching structure of carbohydrates has inherent information potential in biological recognition processes, which enzymes, and proteins in general, can recognise, adapt to, and act upon. Research is focused on structure-function studies of pathogenic bacterial proteins, which participate in oligosaccharide synthesis (glycosyltransferases) or specific recognition (lectins). The former is represented by mycobacterial glycosyltransferases, key enzymes in the biosynthesis of the unusual and well-organized cell wall of Mycobacterium tuberculosis that is responsible for its resistance to most common antibiotics and chemotherapeutic agents. The latter includes molecules that are involved in host-pathogen interactions, for example Pseudomonas aeruginosa lectins, which could be responsible for the high mortality and morbidity of cystic fibrosis patients, enabling the pathogen colonisation of lung alveoli. At present, 2 postgraduate and 4 undergraduate students participate in these projects.

Most important results or innovations

The crystal structures of several lectins from bacteria and fungi have been solved and their thermodynamic and/or kinetic characteristics of oligosaccharide-lectin interactions described. Among them, the structure of PA-IIL, the fucose-binding lectin of P. aeruginosa, has been solved at very high resolution. A new binding mode for carbohydrate, based on the interaction with two calcium ions, was discovered and proposed as the basis for the unusually high affinity of the PA-IIL lectin to its ligand

Selected publications

  • Lameignere, E., Malinovská, L., Sláviková, M., Duchaud, E., Mitchell, E.P., Varrot, A., Šedo, O., Imberty, A., Wimmerová, M.: Structural basis for mannose recognition by a lectin from opportunistic bacteria Burkholderia cenocepacia. Biochem. J. Immediate Publication, doi:10.1042/bj20071276 (2008)
  • Marotte, K., Sabin,C., Préville, C., Moumé-Pymbock, M., Wimmerová, M., Mitchell, E.P., Imberty, A., Roy, R.: X-ray Structures and Thermodynamics of the Interaction of PA-IIL from Pseudomonas aeruginosa with Disaccharide Derivatives. ChemMedChem 2, 1328 – 1338 (2007)
  • Adam, J., Pokorná, M., Sabin, C., Mitchell, E.P., Imberty, A., Wimmerová, M.: Engineering of PA-IIL lectin from Pseudomonas aeruginosa - Unravelling the role of the specificity loop for sugar preference. BMC Struct Biol, BMC Struct Biol. 7:36. (2007)
  • Kirkeby, S., Wimmerová, M., Moe, D., Hansen, A. K.: The mink as an animal model for Pseudomonas aeruginosa adhesion: binding of the bacterial lectins (PA-IL and PA-IIL) to neoglycoproteins and to sections of pancreas and lung tissues from healthy mink. Microbes Infect., 9, (5), 566-73 (2007)
  • Pokorná, M., Cioci, G., Perret. S., Rebuffet, E., Kostlánová, N., Adam, J., Gilboa-Garber, N., Mitchell, E.P., Imberty, A., Wimmerová, M.: Unusual Entropy Driven Affinity of Chromobacterium violaceum Lectin CV-IIL towards Fucose and Mannose, Biochemistry, 45 (24), 7501-7510 (2006)
  • Imberty, A., Mitchell, E.P., Wimmerová, M.: Structural basis of high-affinity glycan recognition by bacterial and fungal lectins, Curr. Opin. Struct. Biol., 15(5), 523-534 (2005) – „9.821“
  • Kostlánová N., Mitchell E.P., Lortat-Jacob H., Oscarson S., Lahmann M., Gilboa-Garber N., Chambat G., Wimmerová M., Imberty A.: The fucose-binding lectin from Ralstonia solanacearum: a new type of beta-propeller architecture formed by oligomerisation and interacting with fucoside, fucosyllactose and plant xyloglucan, Journal of Biological Chemistry, 280, 27839-27849 (2005)
  • Perret, S., Sabin, C., Dumon, C., Pokorná, M., Gautier, C., Galanina, O., Ilia, S., Bovin, N., Nicaise, M., Desmadril, M., Gilboa-Garber, N., Wimmerová, M., Mitchell, E.P., Imberty, A.: Structural basis for the interaction between human milk oligosaccharides and a bacterial protein, Pseudomonas aeruginosa lectin PA-IIL, Biochemical Journal 389 (2), 325-332 (2005)
  • Mitchell, E.P., Sabin, C., Šnajdrová, L., Pokorná, M., Perret, S., Gautier, C., Hofr, C., Gilboa-Garber, N., Koča, J., Wimmerová, M., Imberty, A.: High affinity fucose binding of Pseudomonas aeruginosa lectin PA-IIL: 1.0 Å resolution crystal structure of the complex combined with thermodynamics and computational chemistry approaches, Proteins: Structure, Function, and Bioinformatics 58, 735-746 (2005)
  • Sudakevitz, D., Kostlánová, N., Blatman-Jan, G., Mitchell, E.P., Lerrer, B., Wimmerová, M., Katcoff, D.J., Imberty, A., Gilboa-Garber, N.: A new Ralstonia solanacearum high affinity mannose-binding lectin RS-IIL structurally resembling the Pseudomonas aeruginosa fucose-specific lectin PA-IIL, Molecular Microbiology, 52, 691-700 (2004)
  • Imberty, A., Wimmerová, M., Mitchell, E.P., Gilboa-Garber, N.: Structures of the lectins from Pseudomonas aeruginosa: Insights into molecular basis for host glycan recognition, Microbes and Infection, 6, 221-228 (2004)
  • Wimmerová, M., Mitchell, E., Sanchez, J.-F., Gautier, C., Imberty, A. Crystal structure of fungal lectin : Six-bladed ß -propeller fold and novel fucose recognition mode for Aleuria aurantia lectin. Journal of Biological Chemistry, 278, 27059-27067 (2003).
  • Wimmerová, M., Engelsen, S.B., Bettler, E., Breton, C., Imberty, A. Combining fold recognition and exploratory data analysis for searching for glycosyltransferases in the genome of Mycobacterium tuberculosis. Biochimie, 85, 691-700 (2003).
  • Mitchell, E., Houles, C., Sudakevitz, D., Wimmerová, M., Gautier, C., Pérez, S., Wu, M.A., Gilboa-Garber, N., Imberty, A. Structural basis for oligosaccharide-mediated adhesion of Pseudomonas aeruginosa in the lungs of cystic fibrosis patients. Nature Structure Biology, 12, 918-921 (2002).

Cooperation

  • Centre de Recherches sur les Macromolécules Végétales, CNRS, Grenoble, France
  • European Synchrotron Radiation Facility, Grenoble, France
  • Bar-Ilan University, Faculty of Life Sciences, Ramat Gan, Israel
  • The Royal Veterinary and Agricultural University, Food Technology, Copenhagen, Denmark

Financial support

Research is being supported by grants from the Ministry of Education of the Czech Republic, Gant Agency of the Czech Republic, the French Ministry of Research and the French Cystic Fibrosis Association.

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