Caseinolytic protease P subunit 2 (ClpP2)

Caseinolytic protease P subunit 2 (ClpP2) is a component of the bacterial Clp protease complex, a major ATP-dependent serine protease that ensures protein quality control, stress tolerance, and turnover of regulatory proteins[1][2][3][7]. Structurally, ClpP2 forms part of a barrel-like tetradecamer (14 subunits, often in conjunction with ClpP1) that degrades misfolded, damaged, or regulatory proteins that are translocated into its proteolytic chamber by AAA+ ATPase chaperones such as ClpX or ClpC[1][5][7]. In several pathogenic bacteria (e.g., Mycobacterium tuberculosis, Listeria monocytogenes, Leptospira interrogans, Chlamydia trachomatis), ClpP2 is indispensable for growth, virulence, and adaptation to stress[3][4][6][7]. ClpP2 has emerged as a promising antibiotic target: chemical activators (including ADEPs and certain peptidomimetic boronates) dysregulate the protease, leading to lethal degradation of essential bacterial proteins, while inhibitors can block its proteolytic function[5][3].

Other names

ClpP2Clp protease subunit P2ClpP-2ClpP II

Small-molecule activators (such as ADEPs or Bz-LL) dysregulate or hyperactivate ClpP2, resulting in uncontrolled proteolysis and bacterial death; inhibitors bind active sites to block proteolysis