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A Novel Active DNA Topoisomerase I in Leishmania donovani

2003; Elsevier BV; Volume: 278; Issue: 6 Linguagem: Inglês

10.1074/jbc.m203991200

1083-351X

Héctor Villa, Ana R. Otero Marcos, Rosa M. Reguera, Rafael Balaña‐Fouce, Carlos García‐Estrada, Yolanda Pérez‐Pertejo, Babu L. Tekwani, Peter J. Myler, Kenneth Stuart, Mary‐Ann Bjornsti, David Ordóñez,

Synthesis and Biological Evaluation

A common feature shared by type I DNA topoisomerases is the presence of a "serine, lysine, X, X, tyrosine" motif as conventional enzyme active site. Preliminary data have shown that Leishmania donovani DNA topoisomerase I gene (LdTOP1A) lacked this conserved motif, giving rise to different theories about the reconstitution of an active DNA topoisomerase I in this parasite. We, herein, describe the molecular cloning of a new DNA topoisomerase I gene from L. donovani (LdTOP1B) containing the highly conserved serine, lysine, X, X, tyrosine motif. DNA topoisomerase I activity was detected only when both genes (LdTOP1A and LdTOP1B) were co-expressed in a yeast expression system, suggesting the existence of a dimeric DNA topoisomerase I in Leishmania parasites.