Fenwick Michael K, Ealick Steven E
Department of Chemistry and Chemical Biology, Cornell University , Ithaca, New York 14853, United States.
Biochemistry. 2016 Aug 2;55(30):4135-9. doi: 10.1021/acs.biochem.6b00626. Epub 2016 Jul 22.
The quinolinate synthase of prokaryotes and photosynthetic eukaryotes, NadA, contains a [4Fe-4S] cluster with unknown function. We report crystal structures of Pyrococcus horikoshii NadA in complex with dihydroxyacetone phosphate (DHAP), iminoaspartate analogues, and quinolinate. DHAP adopts a nearly planar conformation and chelates the [4Fe-4S] cluster via its keto and hydroxyl groups. The active site architecture suggests that the cluster acts as a Lewis acid in enediolate formation, like zinc in class II aldolases. The DHAP and putative iminoaspartate structures suggest a model for a condensed intermediate. The ensemble of structures suggests a two-state system, which may be exploited in early steps.
原核生物和光合真核生物的喹啉酸合酶NadA含有一个功能未知的[4Fe-4S]簇。我们报道了嗜热栖热菌NadA与磷酸二羟丙酮（DHAP）、亚氨基天冬氨酸类似物和喹啉酸形成复合物的晶体结构。DHAP呈近乎平面的构象，并通过其酮基和羟基螯合[4Fe-4S]簇。活性位点结构表明，该簇在烯二醇盐形成过程中充当路易斯酸，类似于II类醛缩酶中的锌。DHAP和假定的亚氨基天冬氨酸结构提示了一种缩合中间体模型。这些结构的集合表明存在一个双态系统，这可能在早期步骤中得到利用。
