Targeting Echinococcus multilocularis PIM kinase for improving anti-parasitic chemotherapy
Fig 2
Homologies and structural features of EmPim.
(A) Amino acid sequence alignment of the kinase domains of human Pim-1 (HsPIM1), E. multilocularis Pim (EmPim), human FLT3 kinase (HsFLT3), human haspin kinase (HsHASPIN) and an E. multilocularis haspin kinase ortholog (EmHASPIN1). Residues identical to human Pim-1 are shown in black on grey. Kinase DFG motifs and the hinge regions are marked in red. Black triangles indicate residues known to be involved in the interaction between human Pim-1 and compound CX-6258 (numbered according to human Pim-1). (B) Presence of amino acid residues important for the interaction between human Pim-1 and CX-6258 in different kinases. For each of the 14 known residues of human Pim-1 (HsPIM1), the corresponding residue and position in E. multilocularis Pim (EmPIM), human FLT3 kinase (HsFLT3), human haspin kinase (HsHASPIN), and the E. multilocularis haspin kinase isoform (EmHASPIN1) are shown. Residues identical to those of human Pim-1 are marked in yellow, residues with similar biochemical properties are marked in green. The numbers of identical/similar residues compared to human Pim-1 are listed to the right as well as IC50 values of compounds CX-6258 and SGI-1776 to human enzymes.