Two propellers building a cage
This analysis, down to 2 ngstrm resolution, revealed that ASST indeed contains an extremely short disulfide bond which can presumably only be formed by the action of the disulfide bond formation machinery genetically associated with ASST. This disulfide bridge is a prerequisite for proper folding of this protein and could also play a role in regulating its catalytic activity.
However, these features were almost outweighed by other unusual discoveries: the researchers found a previously never-observed protein structure to catalyze this process. This structure consists of two equal propeller-like parts which contain active sites in the center of the two propellers, built of beta-pleated sheets. Such a structure has never been observed for a sulfotransferase.
How does this two-propeller machine function? To answer this question, the scientists replaced individual amino acids, i.e. building blocks of the protein. In addition, they used molecules acting as sulfuryl-donors and repeated crystallographic analyses. Now they saw that five amino acids containing nitrogen are essential for the function of ASST. They built a reaction cage that accommodates both the donor and the acceptor of the sulfuryl group. Furthermore, during the transfer, the sulfuryl group is directly, covalently bound to a histidine side chain of ASST. Thus, the signal is first transferred from the donor to ASST and subsequently from ASST to the acceptor. Such a ping-pong mechanism is unique in the processes of sulfuryl transfer.
Point of vantage against the bad" E. coli strains
A new structure, a new mechanism this opens up medically relevant perspectives. Goran Malojčić; the first author of this study, explains several interesting points. Since ASST is not present in mammals, the protein could be
|Contact: Prof. Rudi Glockshuber|
ETH Zurich/Swiss Federal Institute of Technology