Today, we have published a comprehensive structural and functional analysis of a (p)ppGpp synthesizing enzyme (a so-called small alarmone synthetase) from S. aureus in the Journal of Biological Chemistry. These enzymes are only found in Gram positive bacteria and thought to respond to cellular stress by producing the alarmone molecule, (p)ppGpp.
Using substrate analogues and product molecules, we were able to trap the enzyme in both the pre-catalytic state (bound to ATP and GTP) as well as in the post-catalytic state (bound to (p)ppGpp). Together, these structures complete our view of the catalytic cycle of this group of enzymes. We also show, using biochemistry, that this enzyme (S. aureus SAS2, RelP) is not regulated allosterically by its product as the other homologous enzyme found in many of these organisms (SAS1, RelQ). Instead, the enzyme appears to be regulated by binding of metal ions, which means that it could respons to minute alterations of the cellular homeostasis.
For more information, read our paper in the Journal of Biological Chemistry.
The article was featured on the cover of the 1 March 2018 issue of the journal.
Manav, M. C., Beljantseva, J., Bojer, M. S., Tenson, T., Ingmer, H., Hauryliuk, V., Brodersen, D. E. (2018) “Structural basis for (p)ppGpp synthesis by the Staphylococcus aureus small alarmone synthetase RelP”, J Biol Chem, 293(9): 3254-64.