The first crystal structure of a phospholipase D
The first crystal structure of a phospholipase D
复制标题
DOI：
10.1016/s0969-2126(00)00150-7
复制
发表时间：
2000-06-15
期刊：
影响因子：
5.7
通讯作者：
Hough, E
中科院分区：
文献类型：
--
作者：
Leiros, I;Secundo, F;Hough, E
背景：磷脂酶D （PLD）超家族包括参与磷脂代谢的酶、核酸酶、毒素和功能未知的病毒包膜蛋白。PLD将磷脂的末端磷酸二酯键水解成磷脂酸和一种亲水成分。磷脂酸是一种与信号转导密切相关的化合物。在磷脂酰胆碱和短链伯醇或仲醇存在下，PLD还催化转磷脂酰化反应。结果：用多波长异常色散（MAD）法测定了单个WO4离子上54 kDa PLD的第一个晶体结构，其分辨率为1.9埃，并将其细化到1.4埃。来自细菌源链霉菌sp.菌株PMF的PLD由一个折叠成两个结构域的单肽链组成。活动站点位于这些域之间的接口上。所提出的结构与鼠伤寒沙门氏菌中已发表的16kda内切酶的结构支持所提出的超家族关系。结论：PLD的结构不仅有助于我们了解细菌、植物和哺乳动物PLD的结构和作用方式，还有助于我们了解多种酶的结构和作用方式，如心磷脂合成酶、磷脂酰丝氨酸合成酶、毒素、核酸内切酶以及功能未知的天花病毒包膜蛋白。这些酶的共同特征是它们可以与磷酸二酯部分结合，并且大多数这些酶以双叶单体或二聚体的形式活跃。
Background: The phospholipase D (PLD) superfamily includes enzymes that are involved in phospholipid metabolism, nucleases, toxins and virus envelope proteins of unknown function. PLD hydrolyzes the terminal phosphodiester bond of phospholipids to phosphatidic acid and a hydrophilic constituent. Phosphatidic acid is a compound that is heavily involved in signal transduction. PLD also catalyses a transphosphatidylation reaction in the presence of phosphatidylcholine and a short-chained primary or secondary alcohol.Results: The first crystal structure of a 54 kDa PLD has been determined to 1.9 Angstrom resolution using the multiwavelength anomalous dispersion (MAD) method on a single WO4 ion and refined to 1.4 Angstrom resolution. PLD from the bacterial source Streptomyces sp. strain PMF consists of a single polypeptide chain that is folded into two domains. An active site is located at the interface between these domains. The presented structure supports the proposed superfamily relationship with the published structure of the 16 kDa endonuclease from Salmonella typhimurium.Conclusions: The structure of PLD provides insight into the structure and mode of action of not only bacterial, plant and mammalian PLDs, but also of a variety of enzymes as diverse as cardiolipin synthases, phosphatidylserine synthases, toxins, endonucleases, as well as poxvirus envelope proteins having a so far unknown function. The common features of these enzymes are that they can bind to a phosphodiester moiety, and that most of these enzymes are active as bi-lobed monomers or dimers.