Biological Sciences Division and Seattle Structural Genomics Center for Infectious Disease, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
Biochem Biophys Res Commun. 2010 Apr 16;394(4):1012-7. doi: 10.1016/j.bbrc.2010.03.112. Epub 2010 Mar 21.
In all organisms adenylate kinases (Adks) play a vital role in cellular energy metabolism and nucleic acid synthesis. Due to differences in catalytic properties between the Adks found in prokaryotes and in the cytoplasm of eukaryotes, there is interest in targeting this enzyme for new drug therapies against infectious bacterial agents. Here we report the 2.1A resolution crystal structure for the 220-residue Adk from Burkholderia pseudomallei (BpAdk), the etiological agent responsible for the infectious disease melioidosis. The general structure of apo BpAdk is similar to other Adk structures, composed of a CORE subdomain with peripheral ATP-binding (ATP(bd)) and LID subdomains. The two molecules in the asymmetric unit have significantly different conformations, with a backbone RMSD of 1.46 A. These two BpAdk conformations may represent 'open' Adk sub-states along the preferential pathway to the 'closed' substrate-bound state.
在所有生物体中，腺嘌呤激酶（Adks）在细胞能量代谢和核酸合成中起着至关重要的作用。由于原核生物和真核生物细胞质中发现的 Adks 在催化特性上存在差异，因此人们有兴趣将这种酶作为针对传染性细菌病原体的新药疗法的靶点。在这里，我们报告了 220 个残基的伯克霍尔德氏菌假单胞菌（BpAdk）腺嘌呤激酶（BpAdk）的 2.1A 分辨率晶体结构，BpAdk 是导致传染性疾病类鼻疽病的病原体。apo BpAdk 的一般结构与其他 Adk 结构相似，由一个 CORE 亚域、外围 ATP 结合（ATP(bd))和 LID 亚域组成。不对称单元中的两个分子具有显著不同的构象，其骨架 RMSD 为 1.46A。这两种 BpAdk 构象可能代表沿着优先途径到“封闭”底物结合状态的“开放”Adk 亚态。
