Adjusting to high temperatures: Researchers discover multifunctional enzyme active in metabolism

Together with the research groups led by Prof. Dr. Oliver Einsle at the Institute of Organic Chemistry and Biochemistry and Prof. Dr. Georg Fuchs from the Institute of Biology II, research groups at the Centre for Biological Signalling Studies (BIOSS), the Spemann Graduate School of Biology and Medicine (SGBM) and the Freiburg Institute of Advanced Studies (FRIAS) have described a fundamentally new type of multifunctional enzyme in this metabolic pathway.

Their new findings have now been published online in the current issue of the journal Nature.

The researchers discovered that the entire field of archaea organisms, which are so-called ancient bacteria, lacks aldolase, which is a key enzyme in gluconeogenesis. In 2010, Dr. Rafael Say and Dr. Georg Fuchs discovered that the enzyme fructose-1,6-bisphosphate can also perform the functions of aldolase, even though the enzyme’s amino acids involved in the aldolase reaction are far removed from the binding site of the substrate.

Dr. Juan Du and Dr. Wei Lü have researched the enzyme fructose-1,6-bisphosphate aldolase/phosphatase (FBPAP) in Prof. Dr. Oliver Einsle’s research group. Using high resolution imaging, they were able to determine three-dimensional structures that revealed a surprisingly complex reaction mechanism in detail. They discovered that it is the actual protein that reorganizes itself around the tightly bound substrate molecule. The entire complex process is controlled by the binding of additional magnesium ions, which are abundantly available in the cell. The binding of these ions completely changes the enzyme in three areas, and its active centre is transformed from an aldolase to a phosphatase.

The researchers from the University of Freiburg characterized this mechanism as a new, multifunctional enzyme. They suspect that similar additional catalytic properties can be found in other proteins but these have not yet been discovered. Regarding FBPAP, this unusual mechanism is believed to be an adjustment to living in higher temperatures, where the starting substances of reaction are instable.