The relationship of angle between N- and C-terminal domains and the activity of thermolysin and elastase

Thermolysin- like proteases (TLPs) belong to subset of Zn-metalloproteases superfamily. The family includes a zinc ion which plays a critival role in the function of enzyme and some different calcium ions to improve stability of the structure. The enzyme function of this family depends on specific conformational motions of active site. The active site in this family is located between N-terminal and C-terminal domain and it has been proposed that TLPs endure a hinge-bending motion during catalysis resulting in “closure” and “opening” of the active-site cleft and raise the probability of structural changes during catalytic process. In this study, the activity of thermolysin compared with elastase achieved from Pseudomonas aeruginosa was investigated and structural changes of the enzymes were investigated by molecular dynamics simulation. The results disclosed that, on one hand- due to reduced hinge-angle- thermolysin tends to greater affinity to the substrate, however, the open mouth of active site represents more freedom of movements of catalytic residues in elastase and therefore catalytic rate constant (kcat) is higher. In general, catalytic efficiency of two enzymes does not reveal much difference at 60 °C.