The Src-homology 2 domain containing protein tyrosine phosphatase- I (SHP- 1) is involved in the pathogenesis of infection with Leishmania. Recently, we identified elongation factor-1alpha (EF-1alpha) from Leishmania donovani as a SHP-1 binding and activating protein [J. Biol. Chem. 277 (2002) 50190]. To characterize this apparent Leishmania virulence factor further, the cDNA encoding L. donovani EF-1alpha was cloned and sequenced. Whereas nearly complete sequence conservation was observed amongst EF-1alpha proteins from trypanosomatids, the deduced amino acid sequence of EF-1alpha a of L. donovani when compared to mammalian EF-1alpha sequences showed a number of significant changes. Protein structure modeling-based upon the known crystal structure of EF-1alpha for Saccharomyces cerevisiae-identified a hairpin loop present in mammalian EF-1alpha and absent from the Leishmania protein which corresponded to a 12 amino acid deletion. Consistent with these structural differences, the sub-cellular distributions of L. donovani EF-1alpha and host EF-1alpha were strikingly different. Interestingly, infection of macrophages with L. donovani caused redistribution of host as well as pathogen EF-1alpha. Since EF-1alpha is essential for survival, the distinct biochemical and structural properties of Leishmania EF-1alpha may provide a novel target for drug development. (C) 2003 Elsevier Science (USA). All rights reserved.