Luton K, Johnson A M
Department of Cell and Molecular Biology, University of Technology, Sydney, Australia.
Biochem Biophys Res Commun. 1997 May 8;234(1):95-100. doi: 10.1006/bbrc.1997.6583.
The gene encoding the DNA polymerase alpha catalytic subunit of the kinetoplastid parasite L. donovani has been isolated, sequenced and compared with other eukaryotic homologues. The coding region is 4020 bp in length and specifies an inferred protein sequence of 1339 amino acids (aa). There is a high level of variability between the human and L. donovani gene sequences, but functional substrate-binding residues identified in humans and yeast appear to also be conserved in this parasite. The discovery of a cysteine-rich region located in the midst of the active sites of the enzyme, which appears to be unique to the Kinetoplastids, and aa differences found between some of the conserved regions implicated in catalytic function, may aid in drug design. The putative DNA binding Zn finger at the C-terminus of the protein appears highly species specific and may have potential as a drug target for blocking enzyme catalysis in the parasite.
编码动基体寄生虫杜氏利什曼原虫DNA聚合酶α催化亚基的基因已被分离、测序，并与其他真核生物同源物进行了比较。编码区长度为4020 bp，推测的蛋白质序列为1339个氨基酸（aa）。人类和杜氏利什曼原虫基因序列之间存在高度变异性，但在人类和酵母中鉴定出的功能性底物结合残基在这种寄生虫中似乎也保守。在该酶活性位点中间发现的一个富含半胱氨酸的区域似乎是动基体所特有的，以及在一些与催化功能相关的保守区域中发现的氨基酸差异，可能有助于药物设计。该蛋白质C末端的假定DNA结合锌指似乎具有高度物种特异性，可能有潜力作为阻断寄生虫酶催化作用的药物靶点。
