Crystal structure of the malic enzyme from Ascaris suum complexed with nicotinamide adenine dinucleotide at 2.3 Ã… resolution
Crystal structure of the malic enzyme from Ascaris suum complexed with nicotinamide adenine dinucleotide at 2.3 Ã… resolution
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DOI：
10.1021/bi0255120
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发表时间：
2002-06-04
期刊：
影响因子：
2.9
通讯作者：
Harris, BG
中科院分区：
文献类型：
--
作者：
Coleman, DE;Rao, GSJ;Harris, BG
猪蛔虫线粒体 NAD-苹果酸酶与 NAD 的二元复合物的结构已通过 X 射线晶体学解析至 2.3 埃的分辨率。该结构类似于与 NAD 复合物测定的人线粒体酶的结构 [Xu, Y., Bhargava, G., Wu, H., Loeber, G., and Tong, L. (1999) Structure 7, 877-889]。该酶是一种四聚体，由具有四个结构域的亚基组成，这些结构域以 NAD 结合形式典型的“开放”结构组织。与人类酶一样，亚基组织是二聚体的二聚体。相对于人类酶，蛔虫酶在其氨基末端含有 30 个额外的残基。这些残基显着增加了促进四聚体形成的相互作用，并产生不同的亚基-亚基相互作用。与哺乳动物酶不同，蛔虫苹果酸酶不受 ATP 调节，并且在该结构中没有观察到 ATP 结合位点。尽管两种酶的活性位点相似，但两者与 NAD 相互作用的残基不同。该结构从机制方面进行了讨论，特别是关于先前获得的动力学和定点诱变实验。
The structure of the Ascaris suum mitochondrial NAD-malic enzyme in binary complex with NAD has been solved to a resolution of 2.3 Angstrom by X-ray crystallography. The structure resembles that of the human mitochondrial enzyme determined in complex with NAD [Xu, Y., Bhargava, G., Wu, H., Loeber, G., and Tong, L. (1999) Structure 7, 877-889]. The enzyme is a tetramer comprised of subunits possessing four domains organized in an "open" structure typical of the NAD-bound form. The subunit organization, as in the human enzyme, is a dimer of dimers. The Ascaris enzyme contains 30 additional residues at its amino terminus relative to the human enzyme. These residues significantly increase the interactions that promote tetramer formation and give rise to different subunit-subunit interactions. Unlike the mammalian enzyme, the Ascaris malic enzyme is not regulated by ATP, and no ATP binding site is observed in this structure. Although the active sites of the two enzymes are similar, residues interacting with NAD differ between the two. The structure is discussed in terms of the mechanism and particularly with respect to previously obtained kinetic and site-directed mutagenesis experiments.