BioXlabs

Antibiotic biosynthetic enzymes

Institution: University of Turku, Department of Biochemistry and Food Chemistry
Project leader: Mikko Metsä-Ketelä
Contact email: mianme[at]utu.fi
Project web pages: www.utu.fi/fi/yksikot/sci/yksikot/biokemia/tutkimus/bk/abe/Sivut/home.aspx

Our research focuses on the chemical biology of secondary metabolites produced by Streptomyces soil bacteria. We are interested in the biosynthesis of aromatic polyketides, an important group of natural products which have been used in medicine and agriculture. Our research combines natural product research, molecular biology, in vitro enzyme chemistry, structural biology, bioinformatics and natural product chemistry. The main goal is to gain insight on the biosynthetic pathways at atomic resolution – to understand the individual biosynthetic reactions and the function and interplay of different enzyme components catalyzing these reactions.

Lysosomal proteins

Institution: University of Turku, Department of Biochemistry and Food Chemistry
Project leader: Pirkko Heikinheimo
Contact email: pirkko.heikinheimo[at]utu.fi
Project web pages: www.sci.utu.fi/biokemia/en/research/biochemistry/alphaman.html

Lysosomal Storage Disorders (LSDs) result from mutations in genes for lysosomal enzymes or for proteins involved in recognition and transport of lysosomal proteins. Carriers of these severe diseases may be overpopulated in common diseases of the elderly. Treatment or prevention of the disease requires molecular level understanding of the lifecycle and formation of lysosomes. We combine X-ray crystallography, structural and proteomic analysis, and cell biology to increase knowledge on the lysosomal proteins and their targeting. The data is collected from structural analysis of known proteins, as well as by studying novel lysosomal proteins and their biology.

Structural basis for chaperone assisted protein folding and assembly of surface virulence organelles, adenosine deaminase type 2 mediated signal transduction, and program cell death in plants

Institution: University of Turku, Department of Chemistry
Project leader: Anton Zavialov
Contact email:anton.zavialov[at]utu.fi

Research in our group is focused on understanding the structural basis for biological processes, such as the chaperone assisted protein folding and assembly, signal transduction, and program cell death.
Molecular chaperones are proteins that assist the non-covalent folding-unfolding and the assembly-disassembly of other macromolecular structures. The periplasmic chaperone/usher machinery, utilizing by Gram-negative pathogens to assemble virulence surface adhesive organelles, is a classical example of a protein folding-assembly catalyst. To reveal the detail mechanism of this process, we determine structures of chaperones, ushers, and organelle subunits as well as chaperone-subunit and chaperone-subunit-usher complexes, identify the conformational changes in chaperones, ushers, and organelle subunits during the assembly process and measure the associated changes in energy. We also study the molecular architecture of the assembled organelles and apply this knowledge in designing novel diagnostics and vaccines against gram-negative pathogens.

Adenosine deaminase related growth factors (ADGFs) is a novel family of extracellular signaling proteins, which perform the signaling function both by controlling the level of the signal messenger, adenosine, and by directly binding to the cell surface receptors. The target of our research is the human adenosine deaminase growth factor, ADA2. Recently we have determined structures of apo-ADA2 and ADA2 complex with transition state analogue and anti-leukemia drug analogue, coformycin. Among our future goals is to reveal the structural basis for ADA2-glycosoaminoglycan and protein receptor interactions as well as ADA2 structure-based design of immune-modulating drugs.

Metacaspases is a family of cystein proteases, which are related to caspases, the executors of program cell death in animals. The study preformed with our collaborators showed that metacaspases play a similar role in plants. We aim at determining the first high-resolution structure of a metacaspase and elucidating the structural basis for its activity.

Protein crystallography

Protein crystallography
Institution: Turku Centre for Biotechnology
Project leader: Tassos Papageorgiou
Contact email: tassos.papageorgiou[at]btk.fi
Project web pages
www.btk.fi/research/research-groups/protein-crystallography
www.btk.fi/crystallography

We use X-ray crystallography as the main technique to study the structure and function of biological macromolecules. In addition, we employ molecular biology and various biophysical and computational techniques to complement our structural studies and provide a better understanding of the structure-function relationship in biological macromolecules. Our current projects include:

1) pathogen-host interactions and oxidative stress,

2) signalling proteins,

3) enzyme stability and function, and

4) radiation damage.

In addition we are running the X-ray crystallography core facility that includes an X-ray generator equipped with focusing mirrors, an Oxford Cryosystems cryostream, and a MAR image plate detector for data collection, several computers for structure determination and analysis, all the latest versions of crystallographic software, and incubators for protein crystallization at various temperatures.

Structural Bioinformatics Laboratory (SBL)

Institution: Department of Biosciences, Åbo Akademi University
Project leaders: Prof. Mark Johnson and Dr. Tiina Salminen
Contact email: mark.johnson[at]abo.fi; tiina.salminen[at]abo.fi
Project web pages: www.abo.fi/institution/en/biokemisbl

Structural Bioinformatics Laboratory (SBL) has a unique
combination of expertise where the independent groups have formed a  tight network, sharing the research facilities and infrastructure. The  emphasis is on multidisciplinary research aiming to solve complex  biological problems related to protein structure and function,  molecular interactions, and gene/protein evolution. In addition, there  is very strong emphasis on education and research training in the  areas of molecular structure determination combining experimental  approaches (x-ray crystallography) with computation methods (molecular  modeling, computational chemistry and bioinformatics).