Structures of Bdellovibrio bacteriovorus phosphoglucose isomerase reveal novel rigidity in the active site of a selected subset of enzymes upon substrate binding.

Glycolysis and gluconeogenesis are central pathways of metabolism across all domains of life. A prominent enzyme in these pathways is phosphoglucose isomerase (PGI) which mediates the interconversion of glucose-6-phosphate and fructose-6-phosphate (F6P). The predatory bacterium Bdellovibrio bacteriovorus leads a complex lifecycle, switching between intraperiplasmic replicative and extracellular "hunter" attack-phase stages. Passage through this complex lifecycle involves different metabolic states. Here we present the unliganded and substrate bound structures of the Bdellovibrio bacteriovorus PGI, solved to 1.74[A] and 1.67 [A], respectively. These structures reveal that an induced-fit conformational change within the active site is not a pre-requisite for the binding of substrates in some PGIs. Crucially, we suggest a phenylalanine residue, conserved across most PGI enzymes but substituted for a glycine in Bdellovibrio and other select organisms, is central to the induced-fit mode of substrate recognition for PGIs. This enzyme also represents the smallest conventional PGI characterised to date and likely represents the minimal requirements for a functional PGI.