Intriguingly, upon PaHisZ binding to R56A-PaHisGS, part of the activity was recovered. Here we employed site-directed mutagenesis, differential scanning fluorimetry (DSF), enzyme kinetics, 31 P-NMR spectroscopy, protein crystallography, and molecular dynamics (MD) simulations to dissect this phenomenon, reveal that other single-and double-mutations at the PaHisGS active site display similar behaviour, and demonstrate how modulation of PaHisGS dynamics by PaHisZ propagates to the active site to affect the chemical step.