Cloning and sequence analysis of the DNA polymerase alpha gene of Leishmania donovani: comparison with the human homologue

Biochem Biophys Res Commun. 1997 May 8;234(1):95-100. doi: 10.1006/bbrc.1997.6583.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • Cloning, Molecular
  • Conserved Sequence
  • Cysteine / chemistry
  • DNA Polymerase II / chemistry
  • DNA Polymerase II / genetics*
  • DNA Polymerase II / metabolism
  • Enzyme Inhibitors / pharmacology
  • Genes, Protozoan*
  • Humans
  • Leishmania donovani / enzymology
  • Leishmania donovani / genetics*
  • Molecular Sequence Data
  • Protein Structure, Secondary
  • Sequence Homology, Amino Acid
  • Zinc Fingers

Substances

  • Enzyme Inhibitors
  • DNA Polymerase II
  • Cysteine

Associated data

  • GENBANK/U78172