V-ATPases的功能及其抑制剂研究进展

V-ATPases作为一类酶,在真核细胞中广泛存在。V-ATPases是一个由多个亚基组成的复合物,主要有两个结构域,分别是位于外周的V1结构域和跨膜的V0结构域。V1结构域可以通过水解ATP供能;而V0结构域是质子的通道。它们发挥作用主要是通过水解ATP供能,泵运H＋进入囊泡腔中或泵H＋出细胞外。V-ATPases定位于细胞器膜及某些特殊细胞的细胞质膜,参与骨吸收、肿瘤的侵袭及耐药等生理及病理过程,因而V-ATPases是治疗骨质疏松、糖尿病及肿瘤等人类疾病的候选分子靶标。目前有许多研究致力于发现新的潜在的特异的V-ATPase抑制剂。

Progress in the functions of V-ATPases and its inhibitors

The vacuolar ATPases （V-ATPases） are a class of enzymes distributed throughout eukaryotes. They are large, multi-subunit complexes organized into two domains, the peripheral V1 domain and the integral Vo domain. Vt domain is responsible for ATP hydrolysis whereas V0 domain carries out proton translocation. V- ATPases provide energy by ATP hydrolysis to pump protons from the cytoplasm to the lumen of vacuoles or into the extracellular environment. They locate in the membrane of intracellular compartments and in the plasma membrane of some specific cells. V-ATPases involve in bone resorption, tumor cell invasion and drug resistance, respectively. Therefore, V-ATPases are thought to be a good molecular target in the treatment of a variety of human diseases, including osteoporosis, diabetes and cancer. Scientists focus on finding novel potential and specific inhibitors of V-ATPase.