Antibiotic acyldepsipeptide (ADEP) targets the bacterial ClpP serine protease and can inhibit the growth of numerous bacterial species by activating/dysregulating the protease activity within the cell. The spirochete Leptospira interrogans harbors two ClpP isoforms (LepClpP1 and LepClpP2). Supplementation of ADEP in the Leptospira growth medium resulted in the inhibition of bacterial growth. The ADEP mediated activation of the LepClpP mixture was dependent on the time allowed for the self-assembly of LepClpP1 and LepClpP2. The dynamic light scattering of the LepClpP mixture in the presence of the ADEP indicated a conformational transformation of the LepClpP machinery. Serine 98, a catalytic triad residue of the LepClpP1 in the LepClpP1P2 heterocomplex, was critical for the ADEP mediated activation. The computational prototype of the LepClpP1P2 structure suggested that the hydrophobic pockets wherein the ADEPs or the physiological chaperone ClpX predominantly dock are exclusively present in the LepClpP2 heptamer. Using the ADEP as a tool, this investigation provides an insight into the molecular function of the LepClpP1P2 in a coalition with its ATPase chaperone LepClpX. The shreds of the evidence illustrated in this investigation verify that ADEP1 possesses the ability to control the LepClpP system in an unconventional approach than the other organisms.

抗生素酰基缩肽 (ADEP) 以细菌 ClpP 丝氨酸蛋白酶为目标，可以通过激活/失调细胞内的蛋白酶活性来抑制多种细菌的生长。螺旋体Leptospira interrogans含有两种 ClpP 亚型（LepClpP1 和 LepClpP2）。在钩端螺旋体中补充 ADEP生长培养基导致细菌生长的抑制。ADEP 介导的 LepClpP 混合物的激活取决于 LepClpP1 和 LepClpP2 允许自组装的时间。在 ADEP 存在下，LepClpP 混合物的动态光散射表明 LepClpP 机制发生了构象转变。丝氨酸 98 是 LepClpP1P2 异源复合物中 LepClpP1 的催化三联体残基，对于 ADEP 介导的激活至关重要。LepClpP1P2 结构的计算原型表明，其中 ADEP 或生理伴侣 ClpX 主要停靠的疏水口袋仅存在于 LepClpP2 七聚体中。使用 ADEP 作为工具，这项研究提供了对 LepClpP1P2 与其 ATPase 伴侣 LepClpX 联合的分子功能的洞察。