Jan Steyaert
Enzymes
VIB Department of Molecular and Cellular Interactions, Vrije Universiteit Brussel

PhD: Vrije Universtiteit Brussel, Belgium, '91 Postdoc: ILRI, Nairobi, Kenya, '93-'94 VIB Group leader since start VIB (1995)

e-mail phone +32 2 629 19 31 ADDRESS

Current team members
Group leaders: Jan Steyaert, Toon Laeremans
Staff scientists: Joris Messens, Wim Versées
Postdoctoral scientists: Alexandre Wohlkönig, An Ranquin, Els Pardon, Goedele Roos, Peter Verheesen, Sameh Soror, Vasundara Srinivasan, Veronica Tamu Dufe
Ph.D. Students: Aleksandra Dziewulska, Bart Van Laer, Cezary Waszczak, David Oyen, Gabriela Vasile, Katarzyna Domanska, Koen Van Laer, Marcus Fislage, Mohamed Wael, Romany Abskharon, Salma Akter, Sarah Triest, Saskia Vanderhaegen, Stefan Münnich
Support personnel: Elke Brosens, Eva Beke, Hassan El Hassan, Karolien Van Belle, Katleen Willibal, Khadija Wahni, Mareike Grabner, Nele Buys, Sarah Haesaerts

Keywords
enzymes - protein structure and conformation - nanocontainers - prodrug activation - nucleoside hydrolases

Science

Nanotools for Biomedical Targets: The Nanotools for Biomedical targets unit, under the supervision of Jan Steyaert, is developing nanobodies as unique molecular tools to study the structure-function relation of a number of biomedical targets for which the structural and/or biophysical investigation remains a challenge. Nanobodies will be used in a systematic way:

• As crystallization aids for the study of quite insoluble proteins, membrane proteins, large protein complexes and proteins harboring intrinsically flexible segments.
• As tools in the study of processes leading to amyloid formation. Nanobodies are used to define and isolate intermediates in these multistep processes and to study the dynamics of these proteins and the culprit mutants involved.
  

Globally, the different Biomedical targets under investigation can be clustered into three research topics: Aggregating Proteins and Amyloidosis, Membrane Proteins, and Protein Assemblies. Considering the diversity and the very competitive context of these research topics, we are systematically searching for strong collaborative partners/networks with expertise in the biomedical/biological context of the target under structural investigation.

Redox Regulation: The Redox regulation team, under the guidance of Joris Messens, specializes in the in vitro reconstitution of thiol/disulfide electron transfer pathways and the study of the kinetics during electron transfer. One of the key aims is to better understand how the recurring thioredoxin motive catalyses so many diverse reactions, from the reduction of oxidized arsenate reductase up to the formation and/or exchange of disulfide bonds during the oxidative protein folding process. Currently, focus goes to three divers thiol/disulfide exchange systems: (i) thioredoxin, (ii) oxidoreductases and their role in protein folding and (iii) arsenate reductases. On the long term, we will exploit our biochemical, structural and quantum chemical expertise in thiol/redox-chemistry along three projects: ‘Co-translational protein folding at the ribosomes’, ‘New drugs for the treatment of Mycobacterium tuberculosis with a clear focus on the unexplored mycothiol/mycoredoxin redox pathway’, and ‘Oxidative stress signal transduction in plants’. For more details visit the Brussels Center for Redox Biology website at http://redox.vub.ac.be.

RNA Modification: The RNA modification team, under the supervision of Wim Versées, specializes in the elucidation of the structure-function relationship of nucleoside and nucleic acid-modifying enzymes, using a combination of physicochemical techniques and protein engineering approaches. For years we have been studying the mechanism of protozoal nucleoside hydrolyses. Currently we shifted focus to the elucidation of the mechanism and 3-dimensional structure of tRNA modifying enzymes and enzyme complexes, both from prokaryotic and eukaryotic origin. We hereby particularly emphasize on enzymes involved in modification of the wobble position. These post-transcriptional tRNA modifications play a primordial role in the translation process as they influence cognate codon recognition, stabilization of the codon-anticodon wobble base pairing and the correct aminoacylation. Our main goal is to characterize the interactions between the proteins in the enzyme complexes, their interaction with the RNA substrates, the chemistry of the reaction and the regulation by external factors. Finally, these studies should contribute to a better understanding of the mechanisms underlying diseases caused by tRNA undermodification, which result in (mitochondrial or cytoplasmic) translation infidelities. For more details, contact Wim Versées.

Go to the  Department's own website for more details.

Press releases
See also press release (19/11/2009): Biologists discover bacterial defense mechanism against aggressive oxygen based on a publication in Science (Depuydt et al.)

Versées W, Spaepen S, Wood M, Leeper F, Vanderleyden J, Steyaert J
Molecular Mechanism of Allosteric Substrate Activation in a Thiamine Diphosphate-dependent Decarboxylase
J BIOL CHEM 282, 35269-78, 2007



Versées W, Barlow J, Steyaert J
Transition-state complex of the purine-specific nucleoside hydrolase of T. vivax: enzyme conformational changes and implications for catalysis
J MOL BIOL 359, 331-46, 2006



Loverix S, Steyaert J
Ribonucleases: from prototypes to therapeutic targets?
CURR MED CHEM 10, 779-785, 2003



Versées W, Decanniere K, Van Holsbeke E, Devroede N, Steyaert J
Enzyme-substrate interactions in the purine-specific nucleoside hydrolase from Trypanosoma vivax
J BIOL CHEM 277, 15938-15946, 2002



Versées W, Decanniere K, Pellé R, Depoorter J, Brosens E, Parkin w, Steyaert J
Structure and function of a novel purine specific nucleoside hydrolase from Trypanosoma vivax
J MOL BIOL 307, 1363- 1379, 2001



Loverix S, Steyaert J
Deciphering the mechanism of RNase T1
METHOD ENZYMOL 341, 305-323, 2001



Loverix S, Winquist A, Strömberg R, Steyaert J
An engineered ribonuclease preferring phosphorothioate RNA.
NAT STRUCT BIOL 5, 365-368, 1998

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