Department of Chemistry and Biochemistry, San Diego State University, 5500 Campanile Drive, San Diego, CA, 92182-1030, USA,
Purinergic Signal. 2011 Mar;7(1):21-45. doi: 10.1007/s11302-010-9214-7. Epub 2011 Jan 21.
The first comprehensive review of the ubiquitous "ecto-ATPases" by Plesner was published in 1995. A year later, a lymphoid cell activation antigen, CD39, that had been cloned previously, was shown to be an ecto-ATPase. A family of proteins, related to CD39 and a yeast GDPase, all containing the canonical apyrase conserved regions in their polypeptides, soon started to expand. They are now recognized as members of the GDA1_CD39 protein family. Because proteins in this family hydrolyze nucleoside triphosphates and diphosphates, a unifying nomenclature, nucleoside triphosphate diphopshohydrolases (NTPDases), was established in 2000. Membrane-bound NTPDases are either located on the cell surface or membranes of intracellular organelles. Soluble NTPDases exist in the cytosol and may be secreted. In the last 15 years, molecular cloning and functional expression have facilitated biochemical characterization of NTPDases of many organisms, culminating in the recent structural determination of the ecto-domain of a mammalian cell surface NTPDase and a bacterial NTPDase. The first goal of this review is to summarize the biochemical, mutagenesis, and structural studies of the NTPDases. Because of their ability in hydrolyzing extracellular nucleotides, the mammalian cell surface NTPDases (the ecto-NTPDases) which regulate purinergic signaling have received the most attention. Less appreciated are the functions of intracellular NTPDases and NTPDases of other organisms, e.g., bacteria, parasites, Drosophila, plants, etc. The second goal of this review is to summarize recent findings which demonstrate the involvement of the NTPDases in multiple and diverse physiological processes: pathogen-host interaction, plant growth, eukaryote cell protein and lipid glycosylation, eye development, and oncogenesis.
1995 年，普莱泽首次全面回顾了无处不在的“外切三磷酸腺苷酶”。一年后，先前已被克隆的一种淋巴细胞激活抗原 CD39 被证明是一种外切三磷酸酶。一个与 CD39 和酵母 GDP 酶相关的蛋白家族，其多肽中都含有典型的apyrase 保守区，很快开始扩张。它们现在被认为是 GDA1_CD39 蛋白家族的成员。由于该家族的蛋白水解核苷三磷酸和二磷酸，因此在 2000 年建立了一个统一的命名法，即核苷三磷酸二磷酸水解酶（NTPDases）。膜结合的 NTPDases 要么位于细胞表面，要么位于细胞内细胞器的膜上。可溶性 NTPDases 存在于细胞质中，可能被分泌。在过去的 15 年中，分子克隆和功能表达促进了许多生物体的 NTPDases 的生化特征的研究，最终导致了最近对哺乳动物细胞表面 NTPDase 和细菌 NTPDase 的外显子结构的确定。本文的第一个目标是总结 NTPDases 的生化、突变和结构研究。由于其水解细胞外核苷酸的能力，调节嘌呤能信号的哺乳动物细胞表面 NTPDases（外切 NTPDases）受到了最多的关注。不太受重视的是细胞内 NTPDases 和其他生物体（如细菌、寄生虫、果蝇、植物等）的 NTPDases 的功能。本文的第二个目标是总结最近的发现，这些发现表明 NTPDases 参与了多种不同的生理过程：病原体-宿主相互作用、植物生长、真核生物细胞蛋白和脂质糖基化、眼睛发育和肿瘤发生。
