Abstract
Both thermophilic and hyperthermophilic enzymes in bacterial and archaeal species are activated above a specific temperature threshold but inactivated at another higher temperature. However, the underlying structural basis for these two heat switches is still unresolved. Here, graph theory was used to test if the temperature-dependent noncovalent interactions and metal bridges as identified in a series of crystal structures of the class II bacterial fructose 1,6-bisphosphate aldolase homodimer or homotetramer with or without natural substrates and products bound could form systematic fluidic grid-like mesh networks with topological grids as thermal rings to regulate their structural thermostability and functional thermoactivity. The results indicated that the second biggest grid in the Thermus aquaticus fructose 1,6-diphosphate aldolase dimer may control the specific temperature threshold to release the swapping flexible active sites at the dimeric interface for heat-evoked activation. Meanwhile, the third biggest grid may serve as a necessary structural motif against heat inactivation. Finally, the smallest grid may act as a stiff thermostable anchor. Its dissociation at the maximal melting temperature threshold may stop the catalytic activity. Taken as a whole, this computational study may render the structural motifs for the optimal growth temperature and the extreme heat stability of hyperthermophiles.