Press release: Unique snapshot of an enzyme in action

Nr. 151/2013 - 10.09.2013

Göttingen scientists unravel fundamental mechanisms of biochemical reactions

(pug) Enzymes are the molecular catalysts of life performing vital metabolic functions in every cell. To date, it has been speculated that enzymes literally bend and break their substrates during biochemical reactions. For the first time, scientists at the Göttingen Center for Molecular Biosciences (GZMB) succeeded in experimentally confirming this hypothesis with certainty. The results of this study were published in the prestigious journal Nature Chemistry.

Led by Professor Kai Tittmann and Professor Ralf Ficner, the Göttingen scientists started off by growing highly ordered protein crystals of the human enzyme transketolase, which plays a pivotal role in human cellular sugar metabolism. They then added natural sugar substrates to these protein crystals. The structures of these enzyme crystals were analysed at particle accelerators located in Berlin, Germany and Grenoble, France. The key researchers at the GZMB involved in this study, Dr. Stefan Lüdtke and Dr. Piotr Neumann, were able to calculate an ultrahigh-resolution structure of the sugar molecule bound within the enzyme just in the moment before it splits into two parts. “This unique snapshot of a working enzyme – at a previously unmatched resolution – reveals without a doubt that the sugar substrate is physically distorted within the enzyme, similar to a workpiece clamped in a bench vice,” explains Prof. Tittmann.

Enzymes are often the site of attack for drugs. That is why these new findings are important for the development of tailor-made, highly specific active agents like those used in cancer therapy. “The enzyme human transketolase investigated in the present study exerts a pivotal function in the metabolism of cancer cells as well,“ notes Prof. Tittmann.

Original publication: Stefan Lüdtke et al.: Sub-Ångström-resolution crystallography reveals physical distortions that enhance reactivity of a covalent enzymatic intermediate. Nature Chemistry. Doi: http://dx.doi.org/10.1038/nchem.1728

Contact address:
Professor Kai Tittmann
Georg August University of Göttingen
Faculty of Biology and Psychology
Göttingen Center for Molecular Biosciences (GZMB)
Ernst-Caspari-Haus, Justus-von-Liebig-Weg 11, 37077 Göttingen, Germany
Phone +49 (551) 39-14430
E-Mail: kai.tittmann@biologie.uni-goettingen.de
Internet: www.uni-goettingen.de/en/sh/198266.html