CLONING AND SEQUENCE-ANALYSIS OF THE DNA-POLYMERASE ALPHA-GENE OF LEISHMANIA-DONOVANI - COMPARISON WITH THE HUMAN HOMOLOG

The gene encoding the DNA polymerase alpha catalytic subunit of the ki netoplastid parasite L. donovani has been isolated, sequenced and comp ared 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. d onovani gene sequences, but functional substrate-binding residues iden tified in humans and yeast appear to also be conserved in this parasit e. 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 Kinetop lastids, and aa differences found between some of the conserved region s implicated in catalytic function, may aid in drug design. The putati ve DNA binding Zn finger at the C-terminus of the protein appears high ly species specific and may have potential as a drug target for blocki ng enzyme catalysis in the parasite. (C) 1997 Academic Press.