An Investigation of Crk Prote in Kinases of Leishmania and the Assessment of Their Potential as Drug Targets

Abstract

Cyclin-dependent kinases (CDKs), exemplified by cdc2, are key regulators of the eukaryotic cell cycle [1]. A number of cdc2-related kinase genes have been isolated from trypanosomatids [2-6]. The present study was designed to identify and analyze cdc2-related protein kinases (CRKs), investigate their regulation mechanisms, and thus their role in regulating the cell cycle of the protozoa Leishmania donovani, the causative agent for Kala-azar and Leishmania mexicana; the causative agent for New world cutaneous leishmaniasis. To achieve this aim, CRK3 protein kinase gene was isolated from a Sudanese strain of L. donovani, designated LdCRK3. It encodes a protein of 311 amino acids with 99.7 % identity with the L. mexicana CRK3 and 49.4% identity with human Hscdc2. Southern blot analysis showed that LdCRK3 is single copy, consistent with the genomic organization of all the so-far identified trypanosomatid protein kinases. The sequence of L. donovani CRK3 has been deposited in GenBankTM under the access number AJ426472.