Reshape to survive

Abstract

Transaldolase is a key enzyme in the pentose phosphate pathway and a potential antibacterial drug target. While studying transaldolase from the pathogen Neisseria gonorrhoeae (NgTAL), Wensien and von Pappenheim et al. determined that NgTAL was redox regulated, but mutagenesis quickly ruled out the presence of a typical intramolecular disulfide. Instead, crystal structures of NgTAL in the oxidized state revealed the formation of an unusual crosslink between Cys38 and Lys8, with an additional oxygen atom between the side chains creating a nitrogen–oxygen–sulfur (NOS) bridge. A structure of NgTAL in the reduced state contained molecular oxygen near Cys38, suggesting that Cys38 is oxidized preceding formation of the crosslink, which was corroborated with mutagenesis and further structural analysis of C38S and K8A variants. NOS bridge Cys38