Hunger-Glaser I, Hemphill A, Shalaby T, Hänni M, Seebeck T
Institute of Cell Biology, University of Bern, Baltzerstrasse 4, CH-3012, Bern, Switzerland.
Gene. 2000 Oct 31;257(2):251-7. doi: 10.1016/s0378-1119(00)00401-7.
Nucleoside diphosphate kinase (NDPK) is a highly conserved, multifunctional enzyme. Its originally described function is the phosphorylation of nucleoside diphosphates to the corresponding triphosphates, using ATP as the phosphate donor and a high-energy phosphorylated histidine residue as the reaction intermediate. More recently, a host of additional functions of NDPK have been discovered. Some of these correlate with the capacity of NDPK to transphosphorylate other proteins, in a manner reminiscent of bacterial two-component systems. Other functions may be mediated by direct DNA-binding of NDPK. This study describes the identification of NDPK from the parasitic protozoon Trypanosoma brucei. The genome of this major disease agent contains a single gene for NDPK. The predicted amino acid sequence of the trypanosomal enzyme is highly conserved with respect to all other species. The protein is constitutively expressed and is present in procyclic and in bloodstream forms. Immunofluorescence and immuno-electron microscopy demonstrate that trypanosomal NDPK (TbNDPK) is predominantly localized in the cell nucleus. Histidine phosphorylation of TbNDPK is essentially resistant to the experimental compound LY266500, a potent inhibitor of histidine phosphorylation of trypanosomal succinyl coenzyme A synthase.
核苷二磷酸激酶（NDPK）是一种高度保守的多功能酶。其最初被描述的功能是利用ATP作为磷酸供体，以一个高能磷酸化组氨酸残基作为反应中间体，将核苷二磷酸磷酸化为相应的三磷酸核苷。最近，人们发现了NDPK的许多其他功能。其中一些功能与NDPK以类似于细菌双组分系统的方式对其他蛋白质进行转磷酸化的能力相关。其他功能可能由NDPK与DNA的直接结合介导。本研究描述了从寄生原生动物布氏锥虫中鉴定出NDPK。这种主要致病原的基因组包含一个NDPK基因。锥虫酶的预测氨基酸序列与所有其他物种相比高度保守。该蛋白组成性表达，存在于前循环型和血流型中。免疫荧光和免疫电子显微镜显示，锥虫NDPK（TbNDPK）主要定位于细胞核。TbNDPK的组氨酸磷酸化对实验化合物LY266500基本具有抗性，LY266500是锥虫琥珀酰辅酶A合成酶组氨酸磷酸化的有效抑制剂。
