The AAA proteins are a family of enzymes that play key roles in diverse dynamic cellular processes, ranging from proteostasis to directional intracellular transport. Dysregulation of AAA proteins has been linked to several diseases, including cancer, suggesting a possible therapeutic role for inhibitors of these enzymes. In the past decade, new chemical probes have been developed for AAA proteins including p97, dynein, midasin, and ClpC1. In this review, we discuss how these compounds have been used to study the cellular functions and conformational dynamics of AAA proteins. We discuss future directions for inhibitor development and early efforts to utilize AAA protein inhibitors in the clinical setting.

中文翻译：

---

使用化学抑制剂探测AAA蛋白的构象动力学和细胞功能。

AAA蛋白是一类酶，在蛋白质动态变化到定向细胞内转运等各种动态细胞过程中均起着关键作用。AAA蛋白的失调与多种疾病（包括癌症）有关，这表明这些酶的抑制剂可能具有治疗作用。在过去的十年中，已经针对AAA蛋白开发了新的化学探针，包括p97，动力蛋白，midasin和ClpC1。在这篇综述中，我们讨论了如何将这些化合物用于研究AAA蛋白的细胞功能和构象动力学。我们讨论了抑制剂开发的未来方向以及在临床环境中利用AAA蛋白抑制剂的早期工作。