Abstract
Proteolytic enzymes play key roles in living organisms. Because of their potentially destructive action of degrading other proteins, their activity must be very tightly controlled. The evolutionarily conserved proteins of the HtrA family are an excellent example illustrating strategies for regulating enzymatic activity, enabling protease activation in response to an appropriate signal, and protecting against uncontrolled proteolysis. Because HtrA homologs play key roles in the virulence of many Gram-negative bacterial pathogens, they are subject to intense investigation as potential therapeutic targets. Model HtrA proteins from bacterium Escherichia coli are allosteric proteins with reasonably well-studied properties. Binding of appropriate ligands induces very large structural changes in these enzymes, including changes in the organization of the oligomer, which leads to the acquisition of the active conformation. Properly coordinated events occurring during the process of HtrA activation ensure proper functioning of HtrA and, consequently, ensure fitness of bacteria. The aim of this review is to present the current state of knowledge on the structure and function of the exemplary HtrA family proteins from Gram-negative bacteria, including human pathogens. Special emphasis is paid to strategies for regulating the activity of these enzymes.